Matrajt Et Al. (2021) - Optimizing Vaccine Allocation For COVID-19 Vaccines Shows The Potential Role of Single-Dose Vaccination

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Optimizing vaccine allocation for COVID-19

vaccines: potential role of single-dose vaccination.
Laura Matrajt,1∗ Julia Eaton,2 Tiffany Leung,1 Dobromir Dimitrov,1,3
Joshua T. Schiffer,1,4 David A. Swan,1 Holly Janes1
1
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
2
School of Interdisciplinary Arts and Sciences, University of Washington, Tacoma, USA
3
Department of Applied Mathematics, University of Washington, Seattle, WA, USA
4
Department of Medicine, University of Washington, Seattle, WA, USA
4
Clinical Research Division, Fred Hutchinson Cancer Research Center, WA, USA
∗
To whom correspondence should be addressed; E-mail: laurama@fredhutch.org
Abstract
Most COVID-19 vaccines require two doses, however with limited vaccine supply, pol-
icymakers are considering single-dose vaccination as an alternative strategy. Using a math-
ematical model combined with optimization algorithms, we determined optimal allocation
strategies with one and two doses of vaccine under various degrees of viral transmission.
Under low transmission, we show that the optimal allocation of vaccine vitally depends on
the single-dose efficacy (SDE). With high SDE, single-dose vaccination is optimal, pre-
venting up to 22% more deaths than a strategy prioritizing two-dose vaccination for older
adults. With low or moderate SDE, mixed vaccination campaigns with complete cover-
age of older adults are optimal. However, with modest or high transmission, vaccinating
older adults first with two doses is best, preventing up to 41% more deaths than a single-
dose vaccination given across all adult populations. Our work suggests that it is imperative
to determine the efficacy and durability of single-dose vaccines, as mixed or single-dose
vaccination campaigns may have the potential to contain the pandemic much more quickly.
Introduction
COVID-19 has killed over 2,400,000 people worldwide as of February 21, 2021 [1]. With sev-
eral vaccines proven highly efficacious (estimated at 94.1%, 95%, 82% and 91.6% for Moderna,
1
NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.
medRxiv preprint doi: https://doi.org/10.1101/2020.12.31.20249099; this version posted April 15, 2021. The copyright holder for this preprint
Pfizer, AstraZeneca, and Sputnik V respectively) against COVID-19 [2, 3, 4, 5], hopes are high
that a return to normal life can soon be possible. Twenty other vaccines are currently in phase
3 clinical trials [6]. Most of these vaccines require two doses given at least three weeks apart
[7]. Since a large proportion of the global population needs to be vaccinated to reduce transmis-
sion and mortality, vaccine supply shortage will be inevitable in the first few months of vaccine
availability. Even in high-income countries, which have secured the largest quantities of vac-
cine, supply will be highly insufficient initially [8]. This situation could be far worse in low-
and middle-income countries (LMIC), where vaccine supplies might arrive at later times and
in smaller quantities, with limited vaccine supply for LMIC risking the public and economic
health of those populations as well as that of the global population [9].
Most of the current vaccine prioritization schedules use two-dose deployments [10], but the
logistics of a two-dose vaccination campaign, which ensures a second dose for those who have
already received one dose, are challenging especially in the context of limited vaccine supply
and shelf-life [11]. In previous outbreaks of other infectious diseases, fractional dosing, where
people receive less than the recommended dosage of vaccine, has been successfully utilized
as a way to stretch vaccine supply. A single-dose campaign of the killed oral cholera vaccine
(which also requires two doses) was deployed in a recent cholera outbreak in Zambia, where the
population was vaccinated with one dose and, months later, high-risk individuals were offered
a second dose [12]. In 2016, in response to a yellow fever outbreak in Angola, Uganda and
the Democratic Republic of Congo, a vaccination campaign with one fifth of the recommended
dosage of the yellow fever vaccine [13] was successfully carried out [14, 13]. If sufficiently
effective, single-dose COVID-19 vaccination is attractive for several reasons: it is easier to im-
plement logistically, potentially less costly, and a larger proportion of the population could be
vaccinated in a fixed amount of time, thereby potentially reaching herd immunity levels and
allowing resumption of key community activities (e.g., reopening schools, restaurants, gyms,
2
etc.) more rapidly [15, 16, 17]. This may be especially true if COVID-19 vaccines not only
reduce disease but also prevent infection and hence onward transmission; these are open ques-
tions and data are still emerging on the full spectrum of vaccine effects [18, 3, 19]. However, the
success of a COVID-19 single-dose vaccination campaign depends on the protection acquired
after one dose of vaccine. There is an intrinsic trade-off with using single-dose vaccination
campaigns achieving greater vaccine coverage, in exchange for a potentially lower level of pro-
tection and/or less durable protection.
In this work, we addressed two questions of public-health importance: 1. Who should be
vaccinated first? and 2. How many doses should individuals receive? Utilizing mathematical
models combined with optimization algorithms, we determined the optimal allocation of avail-
able vaccine doses under a variety of assumptions, and at levels of vaccine efficacy consistent
with estimates from phase 3 efficacy trials. We independently minimized five metrics of infec-
tion and disease burden: cumulative infections, cumulative symptomatic infections, cumulative
deaths, and peak non-ICU and ICU hospitalizations. The last two metrics were chosen as a way
to evaluate healthcare system burden. We showed that mixed vaccination strategies in which
some age groups receive one dose while others receive two doses can achieve the greatest re-
ductions in these metrics under fixed vaccine quantities. Further, our results suggest that the
optimal vaccination strategy depends on the relative efficacy of single- versus full-dose vacci-
nation; on the full spectrum of vaccine effects; on the number of vaccine doses available; and
on the speed of vaccine rollout and the intensity of background transmission. This highlights
the critical importance of continued research to define the level of efficacy conferred by a single
vaccine dose and to evaluate efficacy against not only COVID-19 disease, but SARS-CoV-2
infection and secondary transmission.
3
Results
Because it is expected that vaccine supplies will ramp up considerably over the second half of
2021 and into 2022, and because there is considerable uncertainty around durability of vaccine
protection, we focused on the first few months of vaccine availability and set 6 months for the
duration of our simulations. We built upon our previous model of SARS-CoV-2 transmission
and vaccination [20]. Briefly, we developed a deterministic age-structured mathematical model
with the population of Washington state (7.6 million people) and US demographics divided into
16 age groups with contact rates given in [21], adjusted for reciprocity (Fig. S1). To perform the
vaccine optimization, we collapsed the 16 age-groups into 5 vaccination age-groups: 0–19, 20–
49, 50–64, 65–74, and those 75 and older, aligned with vaccination groups currently considered
by the Centers for Disease Control and Prevention (CDC) [22]. We assumed that at the begin-
ning of our simulations, 20% of the population has pre-existing immunity (through infection)
[23] distributed proportionally to the population, and the SARS-CoV-2 prevalence (number of
current SARS-CoV-2 active infections) was 0.1% of the population [24] (alternative scenarios:
20% pre-existing immunity with different distributions across the population, 10% pre-existing
immunity and 0.05% or 0.3% prevalence, see Sensitivity Analysis and SM). We assumed that
asymptomatic infections are 75% as infectious as symptomatic infections (alternative scenario:

30% as infectious, see Sensitivity Analysis and SM) and confer complete immunity upon re-
covery, over our time horizon of 6 months. Further, we assumed that both naturally-acquired
immunity and vaccine-induced immunity (one- and two-dose) do not wane during our 6 month
time horizon.
We considered a baseline R0 = 3 (alternative scenario R0 = 4, Sensitivity Analysis) with

four levels of social distancing interventions that would affect the contact rates and therefore
SARS-CoV-2 transmission, such that, in combination with the assumed level of pre-existing im-
4
munity, resulted in effective reproductive numbers (defined as the average number of secondary
cases per infectious case in a population made up of both susceptible and non-susceptible hosts)
of Reff = 1.1 (observed in WA state in January 2021 [25]), 1.3, 1.5 and 2.4, respectively, at the
beginning of our simulations (table S3, Fig. S2 and SM). Of course, as vaccination and the epi-
demic process progress, the Reff will change. We evaluated five metrics of disease and healthcare
burden: cumulative infections, cumulative symptomatic infections, cumulative deaths, maxi-

mum number of non-ICU hospitalizations and maximum number of ICU-hospitalizations. State
goals for limiting hospital and ICU beds occupied by COVID-19 patients [26, 27] were used
for result interpretation.
Modeling the vaccine effects
Ongoing phase 3 COVID-19 vaccine trials evaluate vaccine efficacy against laboratory-confirmed
COVID-19, or the multiplicative reduction in per-exposure risk of disease which we denote by
VEDIS . We considered a leaky vaccine (that is, a vaccine that confers partial protection to all
vaccinated individuals) that can have three effects on vaccinated individuals [28]: to reduce the
probability of acquiring a SARS-CoV-2 infection (measured by VESUS ), reduce the probabil-
ity of developing COVID-19 symptoms after infection (measured by VESYMP ), or reduce the
infectiousness of vaccinated individuals upon infection (measured by VEI , Fig. S3A).

Given the efficacy data on two-dose COVID-19 vaccines to date [2, 29, 3, 30], we considered
a main scenario with VEDIS = 90%. Because many combinations of VESUS and VESYMP can
result in the same VEDIS (Fig. S3B), and in advance of definitive data on VESUS or VESYMP for
COVID-19 vaccines, we considered three different vaccine profiles that yield VEDIS = 90%: a
vaccine effect mediated by VESUS only, a vaccine effect mediated by VESYMP only, and a vaccine
effect that is a combination of VESUS and VESYMP (Fig. S3B, Table S1). In the absence of data
on the vaccine effect on infectiousness, we took a conservative approach and assumed VEI = 0
5
(alternative scenario, VEI = 70%, Sensitivity Analysis, SM). Given the limited data to-date
regarding the efficacy of single-dose vaccination of vaccines intended to be given in a two-dose
schedule [31, 4], we considered three “single-dose efficacy” (SDE) scenarios, under our main
scenario where two-dose VEDIS = 90%: low SDE, whereby the single-dose vaccine confers
low efficacy against COVID-19 disease (VEDIS1 =18%); moderate SDE with VEDIS1 = 45%;
and high SDE with VEDIS1 = 72%; corresponding to 20, 50, and 80% of the 90% efficacy
of the full two-dose regimen, respectively. The efficacy of single-dose vaccination against in-
fection and symptoms were assumed to be reduced proportionally. All vaccine effects were
assumed to take effect immediately following each vaccine dose and to remain constant after
the last vaccine dose over the time horizon of 6 months. For two-dose vaccination, we explicitly
modeled vaccination campaigns with the first dose, followed by vaccination campaigns with the
second dose, so that individuals receiving two doses had the protection conferred by single dose
vaccination in the inter-vaccination period.
Modeling vaccination campaigns
We considered the distribution of enough vaccine doses to cover from 10% to 50% of the popu-
lation with a single dose. We simulated vaccination campaigns delivering 150,000 (150K) vac-
cine doses per week, with a maximum of 50% of the population vaccinated with a single dose
of vaccine over a ∼6-month period (our time horizon). This matches current vaccination plans
in the US [32]. An alternative scenario with 300K vaccine doses per week was also explored
(Sensitivity Analysis). These are roughly twice and four times, respectively, the vaccination
rate experienced in the US during the 2009 H1N1 influenza pandemic [33].
Throughout the text, we refer to vaccine coverage as the amount of vaccine available to
cover a percentage of the population with one dose of vaccine. For each vaccination scenario
and disease metric, we denote the optimal strategy as the allocation that was found to minimize
6
a given disease metric, as determined by our optimization routine. We compared the optimal
strategy to two other strategies: a pro-rata strategy in which one-dose vaccination is rolled
out across all adult age groups proportional to their population size (this strategy models an
allocation in which all adults are eligible to be vaccinated and we assumed that all age groups
are equally likely to be vaccinated); and a high-risk strategy in which two-dose vaccination is
allocated to the oldest age groups first and then to younger age groups in decreasing order as
vaccine availability permits (similar to the current prioritization strategy in the US [34]). For
example, with 50% vaccine coverage, under the pro-rata strategy 66.5% of each age group (ex-
cluding children) would receive a single dose of vaccine, and under the high-risk strategy all
of those aged 65 and older and 44% of those aged 50 to 64 years would receive two doses of
vaccine (Fig. S4). We also compared the optimal strategy to a pragmatic strategy, where all
adults aged 65 and older receive two doses of vaccine and all other adults receive a single dose
as coverage permits. The results for this strategy were nearly identical to those from the high-
risk strategy , so we present only the latter set of results. In order to perform the optimization,
we implemented the vaccination campaigns in an identical way for all the allocation strategies
considered: the older age group in a particular strategy is vaccinated first and we moved se-
quentially in decreasing order across the vaccine groups (full details of the implementation are
given in the SM).

To assess parameter uncertainty, for each of the strategies compared and for each outcome,
we ran the model with 1,000 different parameter sets representing the uncertainty surrounding
those parameters we believe would be more likely to affect our results, and removed top and
bottom 2.5% of the simulations to calculate uncertainty intervals (denoted below as 95% UI)
reflecting the uncertainty in the outcomes arising from uncertainty in the parameter estimates
(Uncertainty analysis, SM).

In the main scenario, we considered Reff = 1.1, a vaccine mediated both by VESUS and
7
VESYMP , so that VEDIS = 90% after two doses with VESUS = 70% and VESYMP = 66%, a
vaccination campaign with 150K doses per week, focusing on minimizing COVID-19 deaths.
Results assuming low background viral transmission.
In this section, we assumed that vaccination started under strong social distancing interventions,
resulting in a low background transmission and an Reff = 1.1 or Reff = 1.3, as experienced in WA
state in January 2021 [25]. For low SDE combined with low vaccination coverage (enough
vaccine to cover up to 20% of the population with a single dose), the optimal strategy allocated
two doses of vaccine to the high-transmission group (adults aged 20–49 in our model) and
the high-risk groups (adults aged 65 and older, Figs. 1A, D and 2A). The optimal strategy
averted up to 37% more deaths compared to the pro-rata strategy (Reff =1.3 and 20% coverage
with a single dose, optimal: 54% (95% UI: 51–55) vs. pro-rata: 16% (95% UI: 12–19) deaths
averted compared with no vaccination) and 12% more deaths compared to the high-risk strategy
(Reff =1.1 and 10% coverage, optimal: 42% (95% UI: 35–45) vs. high-risk: 30% (95% UI:27–
31)), Fig. 3A and D. Even at low coverage, the optimal strategy to minimize deaths also resulted
in a significant reduction in overall transmission and hospitalizations (Figs. 2 and S5). As
coverage increased, the optimal strategy prioritized coverage in older adults with two doses of
vaccine (Fig. 1G, J and M), averting over 34% more deaths than the pro-rata strategy , with a
maximum of 45% more deaths averted (Reff =1.3, 40 and 50% coverage, optimal: 68% (95%
UI: 60–70) vs. pro-rata: 22% (95% UI:17–25)), Fig. 3D.
For moderate SDE, the optimal vaccine allocation prioritized the high-risk groups (65 and
older) with mixed vaccination strategies (one and two doses of vaccine) to increase coverage
of these groups when few doses were available, and with two doses of vaccine as coverage
increased (Fig. 1B, E, H, K and N), averting up to 18% more deaths than the pro-rata strategy
(Reff = 1.3, 50% coverage, optimal: 71% (95% UI:63–72) vs. pro-rata: 53% (95% UI:45–
8
55)). However, the optimal strategy provided only a modest gain when compared to the high-
risk strategy, averting an additional 13% of deaths at low coverage (Reff = 1.1, 10% coverage,
optimal: 43% (95% UI:36–47) vs. high-risk: 30% (95% UI:28–32)) and averted a similar
number of deaths for higher levels of coverage (30% or higher), Fig. 3B and E.
In stark contrast, if the vaccine was highly efficacious after one dose, then, for all levels
of coverage, the optimal strategy was almost identical to the the pro-rata strategy (Fig. 1C, F,
I, L and O), and it averted up to 22% more deaths than the high-risk strategy (Reff = 1.1, 10%
coverage, optimal: 53% (95% UI:45–57) vs. high-risk: 31% (95% UI:28–32)), Fig. 3C and F.
While all strategies averted similar number of deaths for high coverage (40 and 50% coverage),
the optimal strategy and the pro-rata strategy had the advantage that they significantly slowed
down viral transmission and as a result, reduced the overall prevalence of infections (Fig. 4C
and F).
Results assuming moderate or high background viral transmission.
We next considered that vaccination started under less strict social distancing interventions,
resulting in moderate or high background transmission with an Reff = 1.5 or Reff = 2.4, as ex-
perienced in WA state early in the pandemic and in November 2020, respectively [25]. Here,
the optimal vaccine allocation was always to directly protect those at highest risk (older adults):
for low and moderate SDE or for a high SDE combined with high coverage, it was optimal to
vaccinate these groups with two doses of vaccine (Fig. 5A, B, D, E, G–O), and if the SDE was
high and few doses were available (≤ 20%) then it was optimal to vaccinate them with a single
dose of vaccine (≤ 20%, Fig. 5C and F) to boost the coverage of that group. If the SDE was low
or moderate, the optimal strategy was almost identical to the high-risk strategy , averting up to
47% more deaths than the pro-rata strategy (low SDE, Reff =1.5, 30% coverage, optimal: 59%
(95% UI:48–63) vs. pro-rata:12% (95% UI:11–15)), Fig. 3G, H, J, K). For high SDE, the gain
9
from optimizing vaccine allocation to improve high-risk strategy was relatively small, averting
up to 12% more deaths (Reff = 1.5, 10% coverage optimal: 41% (95% UI:40–42) vs. high-risk:
29% (95% UI:27–29)) but averted up to 23% more deaths than the pro-rata strategy (Reff =
2.4, 10% coverage, optimal: 36% (95% UI:35–37) vs. pro-rata: 13% (95% UI:12–13) deaths
averted). With moderate viral transmission, the optimal strategy to minimize deaths slightly
reduced the overall prevalence (regardless of the SDE). However, for high viral transmission,
even with enough vaccine to cover 50% of the population, none of the strategies optimized to
minimize deaths reduced transmission (Fig. 4G–L).
Overall, the optimal strategy outperformed the high-risk and the pro-rata strategies the most
under low background transmission and low coverage. For all levels of viral transmission con-
sidered, regardless of the SDE, the epidemic advanced at a faster pace than the vaccination
campaign, evidenced by the fact that the percentage of deaths averted plateaued at 40% (Reff =
1.1), 30% coverage (Reff = 1.3, 1.5) or even 20% coverage (Reff = 2.4), Fig. 3).
Different metrics have different optimal allocation strategies.
The other metrics we considered capture different disease and healthcare burden impacts of the
pandemic, and minimizing each produced a different optimal allocation strategy.
When minimizing outcomes affecting transmission (total infections or total symptomatic

infections) and low SDE, the optimal strategy allocated a mix of one and two doses across
all age groups, Figs. 6 and S6A and D. In contrast, with moderate or high SDE, the optimal
strategy allocated most of the available vaccine to the most active group (adults aged 20–49)
with a single dose, Figs. 6 and S6B, C, E and F).
When minimizing peak non-ICU hospitalizations and for low or moderate SDE, the optimal
strategy prioritized adults aged 65–74 with mixed vaccination strategies to boost coverage of
this age group (Figs. 6 and S6G,H). When minimizing ICU hospitalizations with a vaccine
10
with low or moderate SDE, it was optimal to vaccinate the high-risk group (75 and older) at
high coverage with two doses of vaccine, and all the other groups with mixed allocations of one
and two doses, Figs. 6 and S6J and K. If a single-dose vaccine was highly efficacious, then
for all metrics minimizing severe disease (hospitalizations) or deaths and for nearly all levels
of coverage, the optimal strategy was in fact the pro-rata strategy , (Figs. 6 and S6I, L and O).
However, we noted that even in those scenarios where the optimal and the pro-rata strategies
did not coincide, they averted the same number of deaths.
Interestingly, at this level of viral transmission (Reff = 1.1), the peak hospitalizations (even
in absence of vaccine) stayed below WA state desired thresholds (a maximum of 10% of general
hospital beds occupied by COVID-19 patients and no overflow of the ICU beds, Fig. S5D-I). If
viral transmission increased so that Reff = 1.3, baseline hospitalizations were above the desired
thresholds, and only the optimal strategy achieved Washington state goals of staying below
these thresholds with as little as 20% vaccination coverage, irrespective of the SDE. For higher
coverage, all strategies considered achieved this goal provided that the SDE was moderate or
high (Figs. 7 and S7). However, once Reff ≥1.5, the peak non-ICU and ICU hospitalizations
for all strategies were higher than desired, even at 50% coverage (Fig. S8).
A summary of the optimal allocation strategies for different combinations of SDE and back-
ground transmission for minimizing total infections, hospitalizations and deaths is given in
Fig. 8.
The vaccine profile shapes the optimal allocation strategy.
In this section we analyzed how different vaccine profiles affected the optimal allocation strate-
gies. With a vaccine effect on COVID-19 disease mediated exclusively by a reduction in symp-
toms (high VESYMP ), the optimal strategies for minimizing deaths allocated two doses of vaccine
to older adults (aged 65 and older) for direct protection (Fig. 9A-C), irrespective of the SDE. If
11
the reduction in disease was mediated by both a reduction in symptoms and preventing infec-
tion, or predominately by preventing infection (VESUS ), then for low SDE it was still optimal to
protect higher-risk groups with two doses (Fig. 9D and G). For moderate SDE, directly protect-
ing the higher-risk groups was still optimal, with two doses if the vaccine was mediated by both
effects (moderate VESYMP and moderate VESUS ) and with a single dose if it was exclusively
mediated by preventing infection (Fig. 9E and H) However, if the SDE was high, the pro-rata
strategy performed best (Fig. 9F and I).
A vaccine preventing only symptomatic disease has the potential to prevent only up to 67%
(95% UI: 63–69) of deaths over 6 months compared to 78% (95% UI:72–80) reduction in
mortality if exclusively mediated by preventing infection (Fig. 10C and I).
The vaccine efficacy profile had little effect on the cumulative deaths averted by the high-
risk strategy (regardless of the SDE) but had a major effect on the pro-rata strategy: while
this allocation performed very poorly if the vaccine was exclusively mediated by VESYMP and
low SDE, with 17% (95% UI:15–19) deaths averted (compared with no vaccination) at 50%
coverage, it was much more effective if the vaccine was mediated exclusively by VESUS and
had a high SDE, averting 78% (95% UI:72–80) of the deaths for the same coverage (Fig. 10A
and I).
Moderate protection against infection (VESUS ) was important to all vaccination strategies to
ensure reduction in transmission but especially for the optimal strategy (Fig. S9). A vaccine
acting exclusively by reducing symptoms had a smaller impact on the overall transmission with
a maximum of 41% (95% UI:31–48) cumulative infections averted (high SDE, 50% coverage),
Fig. S9C) while a vaccine that reduced SARS-CoV-2 acquisition could, if optimally allocated,
averted a maximum of 88% (95% UI:83–90) of cumulative infections (high SDE, 50% cover-
age), Fig. S9I.
12
Sensitivity analysis
Results assuming asymptomatic infections are 30% as infectious as symp-
tomatic ones:
Due to the wide range of estimates of the relative infectiousness of asymptomatic infections
to symptomatic ones (ranging from 0.2 to 1 [35]), we repeated our analysis assuming asymp-
tomatic infections were 30% as infectious as symptomatic ones. The most noticeable differ-
ences were found when we analyzed the effect of different vaccine profiles. For low SDE, it
was still optimal to directly protect high-risk groups, with two doses if the vaccine was mediated
by reducing symptoms or if it was mediated by a combination of reducing symptoms and pre-
venting infection, and with a single dose if it was mediated exclusively by preventing infection
(Fig. S10A, D, G). For moderate SDE, mixed allocations were optimal, with more use of single
dose vaccination with a vaccine exclusively mediated by preventing infection (Fig. S10B, E,
H). For high SDE, regardless of the vaccine profile, the pro-rata strategy was in fact, the op-
timal strategy (Fig. S10C, F, I). As expected, if asymptomatic infections are considerably less
infectious then a vaccine mediated exclusively by reducing symptomatic disease has a higher
impact on the overall transmission, preventing as much as 81% (95% UI:76-83) of total infec-
tions (compared to a maximum of 41% (95% UI:31-48) total infections averted in the main
scenario, Figs. S9C) and S11C.
Results assuming 10% pre-existing immunity at the start of vaccination:
We repeated the main analysis assuming 10% of the population has pre-existing immunity at
beginning of vaccination. The results were very similar to those presented in the main sce-
nario, with optimal vaccination strategies favoring single-dose campaigns if the SDE is high
(Fig. S12). In this scenario, the epidemic grows faster than in the main scenario and the as-
13
sumed reduction in contacts presented in Table S3 resulted in Reff =1.3. As a result, the pro-
jected impacts of different strategies are very similar to the ones presented above with Reff =1.3
with the high-risk strategy being optimal for low and moderate SDE when combined with high
coverage and pro-rata strategy being optimal for high SDE irrespective of coverage (Fig. 3D-F).
Results assuming lower or higher infection prevalence at the beginning of

vaccination:
We investigated the effect of infection prevalence (number of current SARS-CoV-2 active in-
fections) at the beginning of vaccination in the optimal allocation strategies by considering 0.05
and 0.3% prevalence at the start of vaccination rollout. The optimal strategies were very similar
irrespective of initial prevalence (Fig. S13). Choosing the optimal strategy mattered most if
vaccination started with lower prevalence: for example, with high SDE and 10% coverage, with
0.05% prevalence, the optimal strategy averted up to 26% more deaths than the high-risk strat-
egy (optimal: 57% (95% UI:47-64) vs high-risk: 31% (95% UI:29-33)), but it only averted a
maximum of 14% more deaths (optimal: 44% (95% UI:41-44) vs high-risk: 30% (95% UI:27-
30)) if vaccination started with 0.3% prevalence. (Fig. S14C and I).
Results assuming more rapid vaccine delivery:
We next investigated the effect of vaccination rate in the optimal allocation strategies. Here, we
assumed that vaccine was rolled out at 300K doses per week (twice as fast as main scenario).
At this rate, 100% of the population can be vaccinated with a single dose over the time span
of six months. For low or high SDE, the optimal strategy was nearly identical to the one de-
scribed in the main scenario. For moderate SDE, the optimal strategy prioritized the high-risk
groups with two doses of vaccine (Fig. S15). With enough vaccine to cover 50% of the popu-
lation and administering 300K doses per week the optimal strategy averted ∼12% more deaths
14
compared to one distributing 150K doses per week. For example, with high SDE and 50% cov-
erage, 87% (95% UI:82–90) and 74% (95% UI:68–77) of deaths were averted compared with
no vaccination, vaccinating at 300K and 150K doses per week respectively, Figs. S16C and 3C.
Furthermore, at this rate and coverage, the optimal strategy to minimize deaths significantly
mitigated transmission irrespective of the SDE, and temporary herd immunity was achieved if
the vaccine had a high SDE (Fig. S16G–I).
Results assuming vaccine efficacy in reducing infectiousness upon infec-

tion:
We identified the optimal allocation strategies assuming that a vaccine, in addition to all the
effects previously described (VEDIS = 90% after two doses with VESUS = 70% and VESYMP =
66%) also reduced infectiousness upon infection by 70% (VEI = 70%) after two doses. For
low and high SDE and for all coverage levels considered, the optimal strategies were very
similar to the ones previously described. For moderate SDE, the optimal allocation was in fact
the pro-rata strategy at low coverage (≤30%), and mixed vaccination strategies that included
full coverage of the older adults with a one and two doses of vaccine (Fig S17) for higher
coverage. All vaccination strategies averted slightly more deaths due to additional vaccine
effects on infectiousness; this was more important at low coverage. With 10% coverage, the
optimal strategies averted a maximum of 12% more deaths compared to the main scenario,
regardless of the SDE (49% (95% UI:41-54), 56% (95% UI:47-61) and 66% (95% UI:56-71)
deaths averted for low, moderate and high SDE in this scenario versus 42% (95% UI:35–45),
43% (95% UI:36–47) and 53% (95% UI:45–57) deaths averted for the main scenario, Figs. 3
and S18, panels A–C. To note, the gains by using the optimal strategy were more evident
in this scenario. For example, with low viral transmission (Reff = 1.3), high SDE and 10%
15
vaccination coverage, the optimal strategy averted up to 37% more deaths than the high-risk
strategy (optimal: 68% (95% UI:55-70) vs. high-risk: 31% (95% UI:29-32) deaths averted)
while the optimal strategy averted a maximum of 16% more deaths than the high-risk strategy
in the main scenario), Figs. 3F and S18F.
Results assuming a different distribution of pre-existing immunity:
In this section we investigated the effect of different distributions of pre-existing immunity on
the optimal allocation strategies. To this end, we considered two additional age distributions
of pre-existing immunity: one using the reported distribution of the number of cases in WA
state [24] as of March 2021 and a second one using the reported distribution of the number of
cases in two Indian states [36] as of July 2020. For each of these distributions, we repeated the
optimization routine (assuming low viral transmission and 150K doses administered weekly).
It is important to note that in both cases, these distributions are potentially over-representing
age groups that are more prone to disease and under-representing those for whom SARS-CoV-2
infections result in a milder or asymptomatic disease. The optimal allocation strategies for both
distributions resulted in nearly identical allocations to those presented in the main section, with
minor differences observed for 20-30% coverage and a moderate SDE (Figs. 1, S19 and S20.)
Results assuming increased transmission due to establishment of new vari-

ants:
We repeated our main analysis assuming a baseline R0 = 4, representing an overall increase

in transmission due to the circulation of new more transmissible variants in the population. We
assumed that vaccines were equally effective against these new variants. Here, the four levels
of social distancing interventions considered (assuming 20% pre-existing immunity) resulted in

effective reproductive numbers of Reff = 1.5, 1.7, 2.0 and 3.2. The optimal allocation strategies
under this scenario were, as expected, identical to those given in the main text when we assumed
16
R0 = 3 and a high level of viral transmission (Figs. 5 and S21). In line with our previous results,
under increased baseline transmission, the optimal strategy averted roughly as many deaths as
the high-risk strategy for almost all levels of coverage with a maximum of 11% more deaths
averted (high SDE, Reff = 1.5, 10% coverage, optimal: 41% (95% UI:40–42) vs. high-risk:
30%, (95% UI:29–31)), and averted a maximum of 46% more deaths than the pro-rata strategy
(low SDE, Reff = 1.5, 30% coverage, optimal: 58% (95% UI:47–62) vs. pro-rata:12% (95%
UI:10–14)), Fig. S22.
Results assuming a lower vaccine efficacy.
We next investigated the effect of vaccine efficacy in our optimal strategies. In this section,
we considered a vaccine with a lower vaccine efficacy, so that VEDIS = 72% after two doses
(similar to that reported in [37]) with VESUS = 49% and VESYMP = 46%. Our results were
not sensitive to this assumption. The optimal allocation strategy was almost identical to that
presented in the main text, with minor differences for moderate SDE and medium coverage
(Figs. 1 and S23). As expected, a lower vaccine efficacy resulted in a lower number of deaths
averted (maximum deaths averted: Reff = 1.1, 50% coverage, high SDE, optimal: 65% (95%
UI:59–68) vs. 74% (95% UI:68–77)), Figs. 3 and S24.
Discussion
COVID-19 vaccination has begun in several countries, and more countries will start in the up-
coming months. As demand will far exceed supply in the initial months of vaccine deployment,
vaccine doses will need to be prioritized. The current strategies of most countries consider
vaccination with full dosage (two doses), but some have proposed vaccinating twice as many
people with a single dose and delaying the second dose [38]. An intense debate about how best
to use the available vaccine is ongoing [15, 39, 40]. Here, we show that there is no universal
17
answer to this question. Pairing a mathematical model parameterized using the evidence to-
date on the efficacy of COVID-19 vaccines with optimization algorithms, we explore the use
of single-dose campaigns and mixed vaccination campaigns, with some people receiving one
dose and others receiving two doses, and we find that the optimal use of resources depends pri-
marily on the level of single-dose efficacy, in agreement with [17]. If a single dose of vaccine
is highly efficacious and introduced under stringent social distancing interventions with low
viral transmission, our results suggest that campaigns that optimally distribute a single vaccine
dose to more people are more effective at averting deaths than a two-dose vaccination campaign
prioritizing subpopulations at high risk of COVID-19 severe disease and death. Previous work
for other infectious diseases [41, 42, 43] has reached similar conclusions. Furthermore, these
results show that vaccinating with a single dose at a faster rate could result in temporary herd
immunity, in agreement with previous work [44]. Importantly, as more vaccine becomes avail-
able, additional vaccination campaigns may be used to cover everyone with the full two doses
of vaccine to provide full protection. In contrast, however, when SARS-CoV-2 transmission is
moderate or high (Reff =1.5 or 2.4 in our model), we find that a two-dose campaign from the
outset is optimal.
In addition, we show that optimal distribution of available vaccine doses across subpopu-
lations depends strongly on the level of transmission. If the ongoing transmission in the com-
munity is well-controlled with stringent non-pharmaceutical interventions in place, the optimal
strategy allocates vaccine to both the high-risk and the high-transmission groups, consistent
with previous work [45]. In contrast, if the level of transmission is moderate or high, it is op-
timal to directly protect those at high risk of severe disease and death, also in agreement with
previous results [46, 20]. Our results highlight the absolute necessity of maintaining social dis-
tancing throughout vaccination [47, 48, 49]: if social distancing interventions are lax before
vaccination is advanced, or if vaccination is not rolled out fast enough, then the current epi-
18
demic wave will be over long before vaccination campaigns are completed and the effect of
vaccination will be limited.
While high vaccine efficacy against COVID-19 has been reported for vaccines requiring
two doses, both for those currently administered in the US (Pfizer and Moderna) and for two
others administered in other parts of the world (Sputnik V and AstraZeneca), other effects
of COVID-19 vaccines require further evaluation, including their effects on preventing SARS-
CoV-2 infection and on infectiousness. To account for these gaps in knowledge, we investigated
the optimal vaccine allocation under three possible vaccine profiles consistent with the observed
vaccine efficacy against disease, and we found that the optimal vaccination strategy depends on
the profile. Our analysis showed that a vaccine that mostly mitigates symptoms but does not
reduce the risk of infection should be prioritized to the oldest age groups at full dosage. In
contrast, the optimal strategy for a vaccine that provides at least moderate protection against
infection includes more balanced dose distribution across age groups with larger proportions
assigned to one-dose vaccinations. Similar to [49], we found that a vaccine that only prevents
disease upon infection will have limited population impact, whereas a vaccine preventing infec-
tion will have a larger effect in reducing population transmission and subsequent morbidity and
mortality. These results underscore the need for thorough studies to evaluate all of the vaccine
effects.
Beyond the impact on infection and disease burden, there are additional arguments for con-
sidering single-dose vaccination, including greater equity achieved in distributing a scarce com-
modity (vaccine) [15], reduced reactogenicity following the first versus the second dose of the
mRNA vaccines [18, 3], and the potential for greater population uptake and adherence to a
single-dose regimen. However, strictly following the two-dose vaccination schedule might also
be important, as the efficacy of a two-dose regimen with a longer interval between doses has not
19
been evaluated systematically in efficacy trials, especially in the context of emerging variants
[50]. Policy-makers would ideally consider these issues in evaluating possible vaccination
strategies.
Here, we report the optimal use of resources as determined by mathematical optimization.
In practice, other factors need to be considered when allocating vaccine. These include differ-
ences in differences in potential behavioral effects associated with vaccination (e.g. behavioral
disinhibition), perceived risk and vaccine hesitancy amongst different age groups, ethical and
logistical considerations. We minimized five different metrics of disease burden, and our results
suggest that the optimal use of vaccine depends on the metric chosen. These metrics were cho-
sen based on the prevailing scientific discussions surrounding COVID-19 vaccine prioritization
[51, 52]. In particular, we chose to optimize cumulative number of deaths as opposed to years
of life lost (YLL), and this resulted in attributing more weight to vaccinating the oldest age
groups, which are at greatest risk of death. Other metrics like YLL would give rise to different
optimal strategies, that may favor younger age groups. Furthermore, new evidence is emerging
about the long-term consequences of COVID-19 disease. This might be an important factor to
incorporate in the metrics of disease burden in future work.
We quantified the advantages and disadvantages of two vaccination prioritization schedules

that closely mimic current guidelines—pro-rata vaccination and vaccination of groups at high
risk of disease—and identified when either of these coincides with our computed optimal allo-
cation strategy, or achieves similar public health impact. While some of the optimal allocation
strategies may be difficult to implement, our results can be used to guide the development of
mixed vaccination strategies, where some subpopulations receive one dose and others receive
two doses, thereby achieving a balance between rapid coverage and full protection of those most
at risk of severe disease and death.
20
Our work has several limitations. Our model assumed that asymptomatic and symptomatic
infections confer equal protection, but asymptomatic infections could result in weaker protec-
tion [53]. We assumed that naturally and vaccine-induced immunity will be at least six months,
but the duration of immunity is not yet known; durable immune responses to the Moderna
mRNA-1273 vaccine have been found through 3 months post-second-dose [54]. Ongoing phase
3 trials will establish the durability of vaccine efficacy, with participants followed 1 to 2 years
post-last vaccination. If immunity is short-lived, then our results are valid only for that time
frame. We also assumed that vaccinating previously infected individuals would have no effect
on their immunity. However, limited data emerging suggests that previous infections might
“prime” the immune response, with only one dose boosting immunity [55]. This would be an
important consideration for future work when evaluating vaccine allocation over longer time
spans with waning immunity. We use age-stratified hospitalization rates based on data from
Wuhan, China [56] and mortality rates based on data from France [57]. These rates strongly
depend on comorbidities (e.g., heart disease, diabetes, etc.) that are country-dependent. It is
then important to determine country-based estimates of these rates to adequately parameterize
models. Deterministic models implicitly result in exponential durations for each disease state,
and they can overestimate infection dynamics. While comparisons with and without vaccina-
tion strategies would not be affected by this, it is possible that our peak hospitalizations are
overestimated and are occurring at a faster pace than in reality. Further, for mathematical and
computational tractability, we used a model that does not account for geographic movement or
complex contact patterns and age was our sole risk factor. In reality, other factors, such as oc-
cupation, have been linked to increased risk of acquisition and severe disease [58, 59]. Because
of systemic social inequalities, several studies have shown that in certain countries people from
racial and minority groups are at increased risk of infection and death from COVID-19 [60].
21
Social distancing interventions are being constantly changed and adapted to new challenges
when transmission is high, but we kept our social distancing interventions fixed for the dura-
tion of the simulations. We included children as possible recipients of vaccine in our analysis,
but vaccines are not currently licensed for individuals under 16 years old. However, vaccine
trials for younger children are underway for the AstraZeneca and Pfizer vaccines [61] and other
vaccine studies in children are being planned, so it is possible that one or more COVID-19
vaccines will be licensed in children within the next 6 months. Importantly, in our model con-
tact rates of children were greatly reduced (by 90% in the contact rates of children at school)
and, while the algorithm can in principle select strategies vaccinating children, it seldom does
so. In order to run the optimization, we considered a fixed implementation scheme to model
vaccination campaigns. We chose this particular implementation because it most closely mim-
ics current vaccine campaigns around the world and it would favor minimizing deaths, but it
is important to note that this implementation scheme would favor the high-risk strategy and
would undermine the pro-rata strategy . In that sense, our results regarding the pro-rata strat-
egy are conservative. Moreover, we used the same implementation for all the disease metrics
considered, but other implementations would be more appropriate for different disease metrics.
Finally, we have determined optimal allocation strategies in the context of considerable uncer-
tainty as to COVID-19 vaccine profiles and vaccine rollout; once vaccine profile, vaccination
rates and coverages for specific countries are known, we welcome validation with more com-
plex models.
There are reports of new and more transmissible SARS-CoV-2 variants first identified in
the UK, South Africa, and Brazil that are spreading rapidly and circulating in several parts
of the globe. It is still unknown how efficacious currently available vaccines will be against
each of these variants, with some vaccines exhibiting a decreased efficacy against some of them
22
[62, 63, 29, 64, 65]. Our results show that if the goal is to minimize transmission as a way to
minimize the spread of these new variants, then it is optimal to vaccinate the high-transmission
groups with one or two doses depending on the SDE. However, a potential concern with single-
dose vaccination is that vaccinating large numbers of people with a regimen with suboptimal
efficacy may allow selection to drive the emergence of new vaccine-resistant variants that can
rise rapidly in frequency [66].
While emerging data suggest that a single dose of the three COVID-19 vaccines (that require
two doses) with regulatory licensure or approval in the US and UK might confer high efficacy
[2, 67, 37], the duration of protection remains unknown. Other vaccines that require two doses,
such as the oral cholera vaccine, are highly effective after a single dose but the protection
provided is short-lived compared to that provided by the full two-dose regimen [68]. If single-
dose immunity lasts for at least 6 months, our results show that if viral transmission is low,
single-dose vaccination campaigns, which are much easier to implement, are the optimal use
of resources in the short term, with the goal to fully vaccinate the entire population in the long
term. In the absence of phase 3 efficacy data on single-dose vaccination, it will be crucial for
vaccine safety systems to capture any breakthrough infections that occur among individuals
receiving vaccination under population campaigns—especially among those receiving a single

dose; and for longitudinal immune responses to be measured in clinical trial participants who
received only one dose. Our work suggests that it is an absolute imperative to quickly and fully
determine the peak and duration of efficacy of single-dose vaccinations, as these data are needed
to support further investigation of mixed vaccination campaigns which have great potential to
more quickly contain the pandemic.
23
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Acknowledgements
We thank Peter Gilbert, Dimitri Leemans, and Natalia Garcı́a-Colı́n for helpful discussions.
Funding: LM was supported by Fred Hutchinson Cancer Research Center discretionary funds
awarded to Peter Gilbert and to the Scientific Computing Infrastructure at Fred Hutch funded
by ORIP grant S10OD028685. HJ was supported by R56AI143418 and R01CA152089 from
the National Institutes of Health. DD, JTS and DAS were supported by NU38OT000297-02
from Centers for Disease Control and Prevention. Author contributions: LM conceived the
study, conducted the analysis and wrote the first draft of the manuscript. JE assisted with the
optimization, analysis, figures and wrote the manuscript. TL, DD, JTD, DAS and HJ contributed
to writing the manuscript. Competing interests: The authors declare no competing interests.
Data availability: Code available at: https://github.com/lulelita/one vs two doses
Figures
32
Low SDE Moderate SDE High SDE
0 20 40 60 80 100 0 20 40 60 80 100 0 20 40 60 80 100

A VEDIS efficacy B VEDIS efficacy C VEDIS efficacy
100 100 100
1 dose
75 2 doses 75 75
50 50 50
10% coverage 25 25 25
0 0 0
D
100
E
100
F
100
75 75 75
50 50 50
20% coverage 25 25 25
0 0 0
G
100
H
100
I
100
75 75 75
50 50 50
30% coverage 25 25 25
0 0 0
J
100
K
100
L
100
75 75 75
50 50 50
40% coverage 25 25 25
0 0 0
M
100
N
100
O
100
75 75 75
50 50 50
50% coverage 25 25 25
0 0 0
0-19 20-49 50-64 65-74 75+ 0-19 20-49 50-64 65-74 75+ 0-19 20-49 50-64 65-74 75+
Age groups Age groups Age groups
Figure 1: Optimal vaccine allocation strategies for minimizing deaths for different vacci-
nation coverages. For each plot, the bars represent the percentage of each age group vaccinated
with a single dose (light blue) and two doses (dark blue) when there is enough vaccine to cover
10% to 50% (as indicated by row) of the population with a single dose. The columns corre-
spond to assumptions that the single-dose efficacy (SDE) is low (left column, VEDIS1 = 18%),
moderate (center column, VEDIS1 = 45%) or high (right column, VEDIS1 = 72%), corresponding
20, 50 or 80% of the 90% efficacy that is assumed following two doses of vaccine, respectively.
Here, we assumed Reff = 1.1.
33
0 20 40 60 80 100 0 20 40 60 80 100 0 20 40 60 80 100

VEDIS efficacy VEDIS efficacy VEDIS efficacy
A B C
100 100 100
1 dose
2 doses
80 80 80
Percentage vaccinated
High-risk
Pro-rata
in each group
60 60 60
40 40 40
20 20 20
0 0 0
0-19 20-49 50-64 65-74 75+ 0-19 20-49 50-64 65-74 75+ 0-19 20-49 50-64 65-74 75+
D E F
500 Baseline 500 500
Optimal
Prevalence of infections
400 High-risk 400 400

Pro-rata
per 100,000
300 300 300
200 200 200
100 100 100
0 0 0
0 50 100 150 0 50 100 150 0 50 100 150
Days Days Days
Figure 2: A–C: Optimal, pro-rata, and high-risk allocation strategies with 20% coverage.
Optimal allocation strategy to minimize deaths (light and dark blue), high-risk (pink) and
pro-rata (green) allocation strategies assuming enough vaccine to cover 20% of the population
with a single dose (10% with two doses). Within each panel, the bars represent the percentage
vaccinated in each vaccination group. D–E: Prevalence of active infections. Prevalence of
active infections (per 100,000) in the absence of vaccine (black), with the optimal allocation
strategy to minimize deaths (blue), the high-risk strategy (pink) or the pro-rata strategy (green)
with enough vaccine to cover 20% of the population with a single dose (10% with two doses).
Shaded areas represent uncertainty intervals. Additional plots for the prevalence of non-ICU
and ICU hospitalizations are shown in Fig.S5. The columns correspond to assumptions that
the single-dose efficacy (SDE) is low (left column, VEDIS1 = 18%), moderate (center column,
VEDIS1 = 45%) or high (right column, VEDIS1 = 72%), corresponding 20, 50 or 80% of the 90%
efficacy that is assumed following two doses of vaccine, respectively. Here, we assumed Reff =
1.1.
34
0 20 40 60 80 100 0 20 40 60 80 100 0 20 40 60 80 100

A100 VEDIS efficacy B100 VEDIS efficacy C100 VEDIS efficacy
Deaths averted (%)
80 80 80
(Reff=1.1)
60 60 60
40 40 40
20 20 20
0 0 0
10 20 30 40 50 10 20 30 40 50 10 20 30 40 50
D100 E100 F100
Deaths averted (%)
80 80 80
(Reff=1.3)
60 60 60
40 40 40
20 20 20
0 0 0
10 20 30 40 50 10 20 30 40 50 10 20 30 40 50
G100 H100 I 100
Deaths averted (%)
80 80 80
(Reff=1.5)
60 60 60
40 40 40
20 20 20
0 0 0
10 20 30 40 50 10 20 30 40 50 10 20 30 40 50
J 100 K100 L100
Optimal
Deaths averted (%)
80 80 80 High-risk
(Reff=2.4)
60 60 60 Pro-rata
40 40 40
20 20 20
0 0 0
10 20 30 40 50 10 20 30 40 50 10 20 30 40 50
Vaccine doses available Vaccine doses available Vaccine doses available
for single-dose coverage (%) for single-dose coverage (%) for single-dose coverage (%)
Figure 3: Percentage of deaths averted for different levels of SARS-CoV-2 transmission.

Percentage of deaths averted for the optimal allocation strategy to minimize deaths (blue), the
high-risk strategy (pink) and the pro-rata strategy (green) with enough vaccine to cover 10-
50% of the population with one dose. Each row represents a different level of SARS-CoV-
2 transmission resulting in Reff = 1.1 (A-C), 1.3 (D-F), 1.5 (G-I) or 2.4 (J-L). Shaded areas
represent uncertainty intervals. The columns correspond to assumptions that the single-dose
efficacy (SDE) is low (left column, VEDIS1 = 18%), moderate (center column, VEDIS1 = 45%)
or high (right column, VEDIS1 = 72%), corresponding 20, 50 or 80% of the 90% efficacy that
is assumed following two doses of vaccine, respectively. Shaded areas represent uncertainty
intervals.
35
A0 20 40
VEDIS efficacy
60 80 100
B0 20 40
VEDIS efficacy
60 80 100
C0 20 40
VEDIS efficacy
60 80 100
of infections
per 100,000 (Reff=1.1)
600 Baseline 600 600

Optimal
400 High-risk 400 400
Pro-rata
per 100,000 (Reff=1.3) Prevalence
200 200 200

0 0 0
0 50 100 150 0 50 100 150 0 50 100 150
D Days E Days F Days
Prevalence of infections Prevalence of infections Prevalence of infections
1500 1500 1500

1000 1000 1000
500 500 500
0 0 0
0 50 100 150 0 50 100 150 0 50 100 150
G Days H Days I Days
per 100,000 (Reff=1.5)
3000 3000 3000

2000 2000 2000
1000 1000 1000
0 0 0
0 50 100 150 0 50 100 150 0 50 100 150
Days Days Days
J K L
per 100,000 (Reff=2.4)
10000 10000 10000

7500 7500 7500
5000 5000 5000
2500 2500 2500
0 0 0
0 50 100 150 0 50 100 150 0 50 100 150
Days Days Days
Figure 4: Prevalence of active infections (per 100,000) for different levels of background
transmission. Prevalence of infections (per 100,000) in the absence of vaccine (black), with the
optimal allocation strategy to minimize deaths (blue), the high-risk strategy (pink) or the pro-
rata strategy (green) with enough vaccine to cover 50% of the population with a single dose
(25% with two doses). Each row represents a different level of SARS-CoV-2 transmission re-
sulting in Reff = 1.1 (A–C), 1.3 (D–F), 1.5 (G–I) or 2.4 (J–L). Shaded areas represent uncertainty
intervals. The columns correspond to assumptions that the single-dose efficacy (SDE) is low
(left column, VEDIS1 = 18%), moderate (center column, VEDIS1 = 45%) or high (right column,
VEDIS1 = 72%), corresponding 20, 50 or 80% of the 90% efficacy that is assumed following two
doses of vaccine, respectively.
36
0 20 40 60 80 100 0 20 40 60 80 100 0 20 40 60 80 100

100 100 100
1 dose
75 2 doses 75 75
50 50 50
10% coverage 25 25 25
0 0 0
D
100
E
100
F
100
75 75 75
50 50 50
20% coverage 25 25 25
0 0 0
G
100
H
100
I
100
75 75 75
50 50 50
30% coverage 25 25 25
0 0 0
J
100
K
100
L
100
75 75 75
50 50 50
40% coverage 25 25 25
0 0 0
M
100
N
100
O
100
75 75 75
50 50 50
50% coverage 25 25 25
0 0 0
0-19 20-49 50-64 65-74 75+ 0-19 20-49 50-64 65-74 75+ 0-19 20-49 50-64 65-74 75+
Figure 5: Optimal vaccine allocation strategies to minimize deaths with different levels of
coverage, assuming Reff =1.5. For each plot, the bars represent the percentage of each age
group vaccinated with a single dose (light blue) and two doses (dark blue) when there is enough
vaccine to cover 10% to 50% (as indicated by row) of the population with a single dose. The
columns correspond to assumptions that the single-dose efficacy (SDE) is low (left column,
VEDIS1 = 18%), moderate (center column, VEDIS1 = 45%) or high (right column, VEDIS1 =
72%), corresponding 20, 50 or 80% of the 90% efficacy that is assumed following two doses of
vaccine, respectively.
37
0 20 40 60 80 100 0 20 40 60 80 100 0 20 40 60 80 100

A
100
B
100
C
100
1 dose
80 2 doses 80 80
(Total infections)
in each group
60 60 60
40 40 40
20 20 20
0 0 0
0-19 20-49 50-64 65-74 75+ 0-19 20-49 50-64 65-74 75+ 0-19 20-49 50-64 65-74 75+
D
100
E
100
F
100
(Symptomatic infections)
80 80 80
in each group
60 60 60
40 40 40
20 20 20
0 0 0
0-19 20-49 50-64 65-74 75+ 0-19 20-49 50-64 65-74 75+ 0-19 20-49 50-64 65-74 75+
G
100
H
100
I
100
80 80 80
in each group
(Peak hosp)
60 60 60
40 40 40
20 20 20
0 0 0
0-19 20-49 50-64 65-74 75+ 0-19 20-49 50-64 65-74 75+ 0-19 20-49 50-64 65-74 75+
J
100
K
100
L
100
80 80 80
(ICU peak hosp)
in each group
60 60 60
40 40 40
20 20 20
0 0 0
0-19 20-49 50-64 65-74 75+ 0-19 20-49 50-64 65-74 75+ 0-19 20-49 50-64 65-74 75+
M
100
N
100
O
100
80 80 80
in each group
60 60 60
(Deaths)
40 40 40
20 20 20
0 0 0
0-19 20-49 50-64 65-74 75+ 0-19 20-49 50-64 65-74 75+ 0-19 20-49 50-64 65-74 75+
Figure 6: Optimal vaccine allocation strategies for different disease metrics with 50% coverage.
Optimal vaccine allocation for a vaccine with VEDIS = 90% and assuming enough vaccine to cover
50% of the population with a single dose (25% with two doses). Each row represents a different disease
metric minimized: cumulative infections (A–C), cumulative symptomatic infections (D–F), non-ICU
peak hospitalizations (G–I), ICU hospitalizations (J–L) and total deaths (M–O). The columns correspond
to assumptions that the single-dose efficacy (SDE) is low (left column, VEDIS1 = 18%), moderate (center
column, VEDIS1 = 45%) or high (right column, VEDIS 381 = 72%), corresponding 20, 50 or 80% of the 90%
efficacy that is assumed following two doses of vaccine, respectively. Here, we assumed Reff = 1.1.
0 20 VE40 60 80 100 0 20 VE40 60 80 100 0 20 VE40 60 80 100

DIS efficacy DIS efficacy DIS efficacy
A B C
Prevalence of non-ICU Prevalence of non-ICU Prevalence of non-ICU Prevalence of non-ICU Prevalence of non-ICU
3000 Baseline 3000 3000

hospitalizaitons
Optimal
2000 High-risk 2000 2000
Pro-rata
1000 1000 1000
0 0 0
0 50 100 150 0 50 100 150 0 50 100 150
3000 3000 3000
hospitalizaitons
2000 2000 2000

1000 1000 1000
0 0 0
0 50 100 150 0 50 100 150 0 50 100 150
3000 3000 3000
hospitalizaitons
2000 2000 2000

1000 1000 1000
0 0 0
0 50 100 150 0 50 100 150 0 50 100 150
J Days K Days L Days
3000 3000 3000
hospitalizaitons
2000 2000 2000

1000 1000 1000
0 0 0
0 50 100 150 0 50 100 150 0 50 100 150
M Days N Days O Days
3000 3000 3000
hospitalizaitons
2000 2000 2000

1000 1000 1000
0 0 0
0 50 100 150 0 50 100 150 0 50 100 150
Days Days Days
Figure 7: Prevalence of non-ICU hospitalizations with Reff =1.3. Prevalence of non-ICU

hospitalizations in absence of vaccine (black), with the optimal allocation strategy to minimize
non-ICU hospitalizations (blue), the high-risk strategy (pink) or the pro-rata strategy (green).
The gray dashed line indicates 10% occupancy of non-ICU beds in WA state. Each row corre-
sponds to a different vaccination coverage, ranging from 10% (A–C) to 50% (M–O) coverage
with a single dose. Shaded areas represent uncertainty intervals. The columns correspond to
assumptions that the single-dose efficacy (SDE) is low (left column, VEDIS1 = 18%), moderate
(center column, VEDIS1 = 45%) or high (right column, VEDIS1 = 72%), corresponding 20, 50 or
80% of the 90% efficacy that is assumed following two doses of vaccine, respectively.
39
A. Cumulative infections B. Peak hospitalizations C. Cumulative deaths
Two doses Two doses

(Reff=1.1-1.3)
Two doses Two doses

(Reff=1.1-1.3)
Two doses to Two doses to One dose to

Background transmission
(Reff=1.1-1.3)
to high- to high- to high- to high-
high- high-
Low
high-
Low
transmission transmission Pro-rata transmission transmission Pro-rata
Low
transmission transmission transmission
and high- and high- and high- and high-
adults adults adults risk adults risk adults
risk adults risk adults
Moderate/ high
Moderate/ high
Moderate/ high
(Reff=1.5-2.4)
(Reff=1.5-2.4)
(Reff=1.5-2.4)
Two doses to Two doses to One dose to
Two doses to Two doses to Two doses to Two doses to Two doses to One dose to
high- high- high-
high-risk high-risk high-risk high-risk high-risk high-risk
transmission transmission transmission
adults adults adults adults adults adults
adults adults adults
Low Moderate High Low Moderate High Low Moderate High

(20% of overall (50% of overall (80% of overall (20% of overall (50% of overall (80% of overall (20% of overall (50% of overall (80% of overall
protection ) protection ) protection ) protection ) protection ) protection ) protection ) protection ) protection )
Single Dose Efficacy Single Dose Efficacy Single Dose Efficacy
Figure 8: Lay summary of vaccine optimization assuming low vaccine coverage. Each box
represents a given single dose vaccine efficacy and background transmission combination. Box
color is light blue if the optimal strategy approximates pro-rata vaccine prioritization and dark
blue if the optimal strategy approximates high-risk vaccine prioritization. A color blend is used
when a hybrid approach is optimal. Text in the boxes describes the optimal approach. All
results imply low vaccine coverage and 20% pre-existing immunity. Panels indicate optimal
allocations for cumulative infections (A), peak hospitalizations (B) and cumulative deaths (C).
40
0 20 40 60 80 100 0 20 40 60 80 100 0 20 40 60 80 100

100
A
100
B
100
C
100
1 dose
2 doses
Vaccine efficacy (%)
80 80 80 80
in each group
60 60 60 60
40 40 40 40
20 20 20 20
0 0 0 0
VESUS VESYMP VEI 0-19 20-49 50-64 65-74 75+ 0-19 20-49 50-64 65-74 75+ 0-19 20-49 50-64 65-74 75+
100
D
100
E
100
F
100
80 80 80 80
in each group
60 60 60 60
40 40 40 40
20 20 20 20
0 0 0 0
VESUS VESYMP VEI 0-19 20-49 50-64 65-74 75+ 0-19 20-49 50-64 65-74 75+ 0-19 20-49 50-64 65-74 75+
100
G
100
H
100
I
100
80 80 80 80
in each group
60 60 60 60
40 40 40 40
20 20 20 20
0 0 0 0
VESUS VESYMP VEI 0-19 20-49 50-64 65-74 75+ 0-19 20-49 50-64 65-74 75+ 0-19 20-49 50-64 65-74 75+
Figure 9: Optimal vaccine allocation to minimize deaths for different vaccine profiles with
50% coverage. Optimal vaccine allocation for minimizing deaths for a vaccine with VEDIS =
90% and assuming enough vaccine to cover 50% of the population with a single dose (25% with
two doses). For each panel (A–I), the bars represent the total percentage of the population in
each vaccination group to be vaccinated, split in those receiving a single dose (light blue) and
those receiving two doses (dark blue). Each row represents a different breakdown of VEDIS =
90% as a function of VESUS and VESYMP . Top row (A–C): VEDIS is mediated by a reduction in
symptoms upon infection. Middle row (D–F): VEDIS is mediated by a combination of reduction
in susceptibility to infection and reduction of symptoms upon infection. Bottom row (G–I):
VEDIS is mediated by a reduction in susceptibility to infection. The columns correspond to
80% of the 90% efficacy that is assumed following two doses of vaccine, respectively. Here, we
assumed Reff = 1.1.
41
0 20 40 60 80 100 0 20 40 60 80 100 0 20 40 60 80 100

100
A100 B100 C100
80 80 80 80
averted (%)
60 60 60 60
Deaths
40 40 40 40
20 20 20 20
0 0 0 0
VESUSVESYMP VEI 10 20 30 40 50 10 20 30 40 50 10 20 30 40 50
100
D100 E100 F100
80 80 80 80
averted (%)
60 60 60 60
Deaths
40 40 40 40
20 20 20 20
0 0 0 0
VESUSVESYMP VEI 10 20 30 40 50 10 20 30 40 50 10 20 30 40 50
100
G100 H100 I 100
80 80 80 80
averted (%)
60 60 60 60
Deaths
40 40 40 40
Optimal
20 20 20 20 High-risk
Pro-rata
0 0 0 0
VESUSVESYMP VEI 10 20 30 40 50 10 20 30 40 50 10 20 30 40 50
Figure 10: Percentage of deaths averted for different vaccine profiles. Percentage of deaths
averted for the optimal allocation strategy to minimize deaths (blue), the high-risk strategy
(pink) and the pro-rata strategy (green) with enough vaccine to cover 10–50% of the popula-
tion with one dose. Each row represents a different breakdown of VEDIS = 90% as a function
of VESUS and VESYMP . Top row (A–C): VEDIS is mediated by a reduction in symptoms upon
infection. Middle row (D–F): VEDIS is mediated by a combination of reduction in susceptibility
to infection and reduction of symptoms upon infection. Bottom row (G–I): VEDIS is medi-
ated by a reduction in susceptibility to infection. The columns correspond to assumptions that
efficacy that is assumed following two doses of vaccine, respectively. Shaded areas represent
uncertainty intervals. Here, we assumed Reff = 1.1.
42
Supplemental figures
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E P
Vaccination 1st dose
P I H RH
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hc C
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ICU RC
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(1 (1 VESYMP1 )k) E
A <latexit sha1_base64="RhUCHLc22hi9T1D6Nk+A+sHBA0Q=">AAAB63icbVBNSwMxEJ2tX7V+VT16CRbBU8mKoseKF49VrC20S8mm2TY0yS5JVihL/4IXD4p49Q9589+YbfegrQ8GHu/NMDMvTAQ3FuNvr7Syura+Ud6sbG3v7O5V9w8eTZxqylo0FrHuhMQwwRVrWW4F6ySaERkK1g7HN7nffmLa8Fg92EnCAkmGikecEptL99d9v1+t4TqeAS0TvyA1KNDsV796g5imkilLBTGm6+PEBhnRllPBppVealhC6JgMWddRRSQzQTa7dYpOnDJAUaxdKYtm6u+JjEhjJjJ0nZLYkVn0cvE/r5va6CrIuEpSyxSdL4pSgWyM8sfRgGtGrZg4Qqjm7lZER0QTal08FReCv/jyMnk8q/sXdXx3XmvgIo4yHMExnIIPl9CAW2hCCyiM4Ble4c2T3ov37n3MW0teMXMIf+B9/gBV9I23</latexit>
RA1
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A1
(1 h)
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(1 VESUS1 ) I
R1
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S1 E1
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<latexit sha1_base64="gTQdEaIDAAmprX+s05bl3BNMfxo=">AAAB6nicbVBNS8NAEJ3Ur1q/qh69LBbBU0nEoseCCB4r2g9oQ9lsN+3SzSbsToQS+hO8eFDEq7/Im//GbZuDtj4YeLw3w8y8IJHCoOt+O4W19Y3NreJ2aWd3b/+gfHjUMnGqGW+yWMa6E1DDpVC8iQIl7ySa0yiQvB2Mb2Z++4lrI2L1iJOE+xEdKhEKRtFKD7d9r1+uuFV3DrJKvJxUIEejX/7qDWKWRlwhk9SYrucm6GdUo2CST0u91PCEsjEd8q6likbc+Nn81Ck5s8qAhLG2pZDM1d8TGY2MmUSB7YwojsyyNxP/87ophtd+JlSSIldssShMJcGYzP4mA6E5QzmxhDIt7K2EjaimDG06JRuCt/zyKmldVL1a1b2/rNTdPI4inMApnIMHV1CHO2hAExgM4Rle4c2Rzovz7nwsWgtOPnMMf+B8/gC5141f</latexit>
h(1 c)
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(1 VESYMP1 )k E
P
H
Vaccination 2nd dose
H1 RH1
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<latexit sha1_base64="7KH6tG6+zHE6T5DRP4yGy6TNJOU=">AAAB6nicbVBNS8NAEJ3Ur1q/qh69LBbBU0nEoseClx4r2g9oQ9lsJ+3SzSbsboQS+hO8eFDEq7/Im//GbZuDtj4YeLw3w8y8IBFcG9f9dgobm1vbO8Xd0t7+weFR+fikreNUMWyxWMSqG1CNgktsGW4EdhOFNAoEdoLJ3dzvPKHSPJaPZpqgH9GR5CFn1FjpoTHwBuWKW3UXIOvEy0kFcjQH5a/+MGZphNIwQbXueW5i/Iwqw5nAWamfakwom9AR9iyVNELtZ4tTZ+TCKkMSxsqWNGSh/p7IaKT1NApsZ0TNWK96c/E/r5ea8NbPuExSg5ItF4WpICYm87/JkCtkRkwtoUxxeythY6ooMzadkg3BW315nbSvql6t6t5fV+puHkcRzuAcLsGDG6hDA5rQAgYjeIZXeHOE8+K8Ox/L1oKTz5zCHzifP75pjWI=</latexit>
I1
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P1
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hc C
ICU1
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RC1
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<latexit sha1_base64="Fzk+E95Ef5Qx3PcG6QM+yZIzHLI=">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</latexit>
(1 (1 VESYMP2 )k) E
A <latexit sha1_base64="5Mn+SKv21UkdCHn6PETVkqJS29c=">AAAB63icbVBNS8NAEJ3Ur1q/qh69LBbBU0mKoseKF49V7Ae0oWy2m3bp7ibsboQS+he8eFDEq3/Im//GTZqDtj4YeLw3w8y8IOZMG9f9dkpr6xubW+Xtys7u3v5B9fCoo6NEEdomEY9UL8CaciZp2zDDaS9WFIuA024wvc387hNVmkXy0cxi6gs8lixkBJtMergZNobVmlt3c6BV4hWkBgVaw+rXYBSRRFBpCMda9z03Nn6KlWGE03llkGgaYzLFY9q3VGJBtZ/mt87RmVVGKIyULWlQrv6eSLHQeiYC2ymwmehlLxP/8/qJCa/9lMk4MVSSxaIw4chEKHscjZiixPCZJZgoZm9FZIIVJsbGU7EheMsvr5JOo+5d1t37i1rTLeIowwmcwjl4cAVNuIMWtIHABJ7hFd4c4bw4787HorXkFDPH8AfO5w9XeI24</latexit>
RA2
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A2
(1 h)
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(1 VESUS2 ) I
R2
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E2
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S2
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h(1 c)
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(1 VESYMP2 )k E
H
P
P2 I2 H2 RH2
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hc C
ICU2
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RC2
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Figure S1: Diagram of the SEIR model with vaccination with one or two doses of vaccine.
Age indices have been omitted for clarity.
1
Home Work Other School

A B C locations D
0-5 1.5
5-10 3 5
10-15 1.00
15-20
20-25 4
25-30 1.0 0.75
30-35 2
Reff = 1.1 35-40
40-45 3
45-50 0.50 2
50-55 0.5 1
55-60
60-65 0.25 1
65-70
70-75
+75 0.0 0.00 0 0
F G H I
0-5 1.5
5-10 3 5
10-15 1.00
15-20
20-25 4
25-30 1.0 0.75
30-35 2
Reff = 1.3 35-40
40-45 3
45-50 0.50 2
50-55 0.5 1
55-60
60-65 0.25 1
65-70
70-75
+75 0.0 0.00 0 0
K L M N
0-5 1.5
5-10 3 5
10-15 1.00
15-20
20-25 4
25-30 1.0 0.75
30-35 2
Reff = 1.5 35-40
40-45 3
45-50 0.50 2
50-55 0.5 1
55-60
60-65 0.25 1
65-70
70-75
+75 0.0 0.00 0 0
P Q R S
0-5 1.5
5-10 3 5
10-15 1.00
15-20
20-25 4
25-30 1.0 0.75
30-35 2
Reff = 2.4 35-40
40-45 3
45-50 0.50 2
50-55 0.5 1
55-60
60-65 0.25 1
65-70
70-75
+75 0.0 0.00 0 0
0-5
5-10
10-15
15-20
20-25
25-30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
+75
0-5
5-10
10-15
15-20
20-25
25-30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
+75
0-5
5-10
10-15
15-20
20-25
25-30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
+75
0-5
5-10
10-15
15-20
20-25
25-30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
+75
Figure S2: Modified contact matrices considered in our simulations. The contact matrices
given in [21] were modified with the multipliers given in table S3 for each of the four scenarios
of viral transmission considered in our simulations, resulting in an Reff = 1.1 (A-D), 1.3 (F-I),
1.5 (K-N), and 2.4 (P-S).
2
Figure S3: A: Different vaccine effects modeled. A vaccine can reduce the probability of
infection, denoted by VESUS . In addition, it can reduce the probability of developing symptoms
once infected, denoted VESYMP . Finally, it can reduce the infectiousness of a vaccinated per-
son upon infection, denoted VEI . We assumed that VEDIS can be expressed as a combination of
VESUS and VESYMP (see text). B: Level curves for VEDIS as a function of VESUS and VESYMP .
The light blue lines indicate the efficacies VEDIS1 obtained after a first dose of vaccine consid-
ered in the main analysis. The dark blue line indicates the vaccine efficacy obtained after the
full dosage (two doses) VEDIS = 90%.
3
A Optimal B High-risk C Pro-rata

100 100 100
1 dose High-risk Pro-rata
2 doses
Percentage vaccinated in each group

80 80 80
60 60 60
40 40 40
20 20 20
0 0 0
0-19 20-49 50-64 65-74 75+ 0-19 20-49 50-64 65-74 75+ 0-19 20-49 50-64 65-74 75+
Figure S4: Example of the A. optimal, B. high risk and C. pro-rata strategies. Here, we assumed
enough vaccine to cover 50% of the population. The optimal strategy allocates vaccine as
determined by our optimization routine. The high-risk strategy allocates two doses of vaccine
starting with the oldest age group and then to other age groups in decreasing order. The pro-rata
strategy allocates one-dose of vaccine to all the adult groups in the population proportional to
their size.
4
0 20 40 60 80 100 0 20 40 60 80 100 0 20 40 60 80 100

A B C
100 100 100
1 dose
80 2 doses 80 80
High-risk
in each group
60 Pro-rata 60 60
40 40 40
20 20 20
0 0 0
0-19 20-49 50-64 65-74 75+ 0-19 20-49 50-64 65-74 75+ 0-19 20-49 50-64 65-74 75+
D E F
1200 1200 1200
Prevalence of non-ICU
hospitalizaitons
1000 1000 1000

Baseline
800 Optimal 800 800
600 High-risk 600 600
Pro-rata
400 400 400
200 200 200
0 0 0
0 50 100 150 0 50 100 150 0 50 100 150
Days Days Days
G H I
1250 1250 1250
Prevalence of ICU
hospitalizations
1000 Baseline 1000 1000

750 Optimal 750 750
High-risk
500 Pro-rata 500 500
250 250 250
0 0 0
0 50 100 150 0 50 100 150 0 50 100 150
Days Days Days
Figure S5: A–C: Optimal, pro-rata and high-risk strategies to minimize deaths with
enough vaccine to cover 20% of the population with a single dose (10% with two doses).
Optimal (light and dark blue), high-risk (pink) and pro-rata (green) allocation strategies. Within
each panel, the bars represent the percentage vaccinated in each vaccination group. D–F: Preva-
lence of non-ICU hospitalizations. Prevalence of non-ICU hospitalizations in absence of vac-
cine (black), with the optimal allocation strategy to minimize deaths (blue), high-risk strategy
(pink) or the pro-rata strategy (green), the gray dashed line indicates the 10% occupancy of
non-ICU beds in WA state. G–I: Prevalence of ICU hospitalizations. Prevalence of non-ICU
hospitalizations in absence of vaccine (black), with the optimal allocation strategy to minimize
deaths (blue), the high-risk strategy (pink) or the pro-rata strategy (green), the gray dashed
line indicates the total number of ICU beds in WA state. Shaded areas represent uncertainty
intervals. The columns correspond to assumptions that the single-dose efficacy (SDE) is low
(left column, VEDIS1 = 18%), moderate (center column, VEDIS1 = 45%) or high (right column,
VEDIS1 = 72%), corresponding 20, 50 or 80% of the 90% efficacy that is assumed following two
doses of vaccine, respectively.
5
0 20 40 60 80 100 0 20 40 60 80 100 0 20 40 60 80 100

A
100
B
100
C
100
1 dose
80 2 doses 80 80
(Total infections)
in each group
60 60 60
40 40 40
20 20 20
0 0 0
0-19 20-49 50-64 65-74 75+ 0-19 20-49 50-64 65-74 75+ 0-19 20-49 50-64 65-74 75+
D
100
E
100
F
100
(Symptomatic infections)
80 80 80
in each group
60 60 60
40 40 40
20 20 20
0 0 0
0-19 20-49 50-64 65-74 75+ 0-19 20-49 50-64 65-74 75+ 0-19 20-49 50-64 65-74 75+
G
100
H
100
I
100
80 80 80
in each group
(Peak hosp)
60 60 60
40 40 40
20 20 20
0 0 0
0-19 20-49 50-64 65-74 75+ 0-19 20-49 50-64 65-74 75+ 0-19 20-49 50-64 65-74 75+
J
100
K
100
L
100
80 80 80
(ICU peak hosp)
in each group
60 60 60
40 40 40
20 20 20
0 0 0
0-19 20-49 50-64 65-74 75+ 0-19 20-49 50-64 65-74 75+ 0-19 20-49 50-64 65-74 75+
M
100
N
100
O
100
80 80 80
in each group
60 60 60
(Deaths)
40 40 40
20 20 20
0 0 0
0-19 20-49 50-64 65-74 75+ 0-19 20-49 50-64 65-74 75+ 0-19 20-49 50-64 65-74 75+
Figure S6: Optimal vaccine allocation strategies for different disease metrics with 20% coverage.
Optimal vaccine allocation for a vaccine with VEDIS = 90% and assuming enough vaccine to cover
20% of the population with a single dose (10% with two doses). Each row represents a different disease
metric minimized: cumulative infections (A–C), cumulative symptomatic infections (D–F), non-ICU
peak hospitalizations (G–I), ICU hospitalizations (J–L) and total deaths (M–O). The columns correspond
to assumptions that the single-dose efficacy (SDE) is low (left column, VEDIS1 = 18%), moderate (center
column, VEDIS1 = 45%) or high (right column, VEDIS 6 1 = 72%), corresponding 20, 50 or 80% of the 90%
efficacy that is assumed following two doses of vaccine, respectively. Here, we assumed Reff = 1.1.
0 20 VE40 60 80 100 0 20 VE40 60 80 100 0 20 VE40 60 80 100

DIS efficacy DIS efficacy DIS efficacy
A B C
3000 3000 3000
Prevalence of ICU
Baseline
hospitalizations
Optimal
2000 High-risk 2000 2000
Pro-rata
1000 1000 1000
0 0 0
0 50 100 150 0 50 100 150 0 50 100 150
3000 3000 3000
Prevalence of ICU
hospitalizations
2000 2000 2000

1000 1000 1000
0 0 0
0 50 100 150 0 50 100 150 0 50 100 150
3000 3000 3000
Prevalence of ICU
hospitalizations
2000 2000 2000

1000 1000 1000
0 0 0
0 50 100 150 0 50 100 150 0 50 100 150
J Days K Days L Days
3000 3000 3000
Prevalence of ICU
hospitalizations
2000 2000 2000

1000 1000 1000
0 0 0
0 50 100 150 0 50 100 150 0 50 100 150
M Days N Days O Days
3000 3000 3000
Prevalence of ICU
hospitalizations
2000 2000 2000

1000 1000 1000
0 0 0
0 50 100 150 0 50 100 150 0 50 100 150
Days Days Days
Figure S7: Prevalence of ICU hospitalizations with Reff =1.3. Prevalence of ICU hospital-
izations in absence of vaccine (black), with the optimal allocation strategy to minimize ICU
hospitalizations (blue), the high-risk strategy (pink) or the pro-rata strategy (green). The gray
dashed line indicates the total number of ICU beds in WA state. Each row corresponds to a
different vaccination coverage, ranging from 10% (A–C) to 50% (M–O) coverage with a single
dose. Shaded areas represent uncertainty intervals. The columns correspond to assumptions that
efficacy that is assumed following two doses of vaccine, respectively. Here, we assumed Reff =
1.1.
7
0 20 40 60 80 100 0 20 40 60 80 100 0 20 40 60 80 100

A B C
100 100 100
1 dose
2 doses
80 80 80
High-risk
Pro-rata
in each group
60 60 60
40 40 40
20 20 20
0 0 0
0-19 20-49 50-64 65-74 75+ 0-19 20-49 50-64 65-74 75+ 0-19 20-49 50-64 65-74 75+
D E F
6000 Baseline 6000 6000
Optimal
5000 5000 5000
Prevalence of non-ICU
High-risk
Pro-rata
hospitalizaitons
4000 4000 4000

3000 3000 3000
2000 2000 2000
1000 1000 1000
0 0 0
0 50 100 150 0 50 100 150 0 50 100 150
Days Days Days
Figure S8: A–C: Optimal strategy to minimize non-ICU hospitalizations, pro-rata and
high-risk strategies with enough vaccine to cover 50% of the population with a single dose
(25% with two doses) with Reff =1.5. Optimal allocation strategy to minimize peak non-ICU
hospitalizations (light and dark blue), high-risk (pink) and pro-rata (green) strategies. Within
each panel, the bars represent the percentage vaccinated in each vaccination group. D–F: Preva-
lence of non-ICU hospitalizations. Prevalence of non-ICU hospitalizations in absence of vac-
cine (black), with the optimal allocation strategy to minimize non-ICU hospitalizations (blue),
the high-risk strategy (pink) or the pro-rata strategy (green). The gray dashed line indicates
10% occupancy of non-ICU beds in WA state. Shaded areas represent uncertainty intervals.
The columns correspond to assumptions that the single-dose efficacy (SDE) is low (left col-
umn, VEDIS1 = 18%), moderate (center column, VEDIS1 = 45%) or high (right column, VEDIS1
= 72%), corresponding 20, 50 or 80% of the 90% efficacy that is assumed following two doses
of vaccine, respectively.
8
0 20 40 60 80 100 0 20 40 60 80 100 0 20 40 60 80 100

100
A100 B100 C100
80 80 80 80
Total infections
averted (%)
60 60 60 60
40 40 40 40
20 20 20 20
0 0 0 0
VESUSVESYMP VEI 10 20 30 40 50 10 20 30 40 50 10 20 30 40 50
100
D100 E100 F100
80 80 80 80
Total infections
averted (%)
60 60 60 60
40 40 40 40
20 20 20 20
0 0 0 0
VESUSVESYMP VEI 10 20 30 40 50 10 20 30 40 50 10 20 30 40 50
100
G100 H100 I 100
80 80 80 80
Total infections
averted (%)
60 60 60 60
40 40 40 40
Optimal
20 20 20 20 High-risk
Pro-rata
0 0 0 0
VESUSVESYMP VEI 10 20 30 40 50 10 20 30 40 50 10 20 30 40 50
Figure S9: Percentage of cumulative infections averted for different vaccine profiles. Per-
centage of cumulative infections averted for the optimal allocation strategy to minimize in-
fections (blue), the high-risk strategy (pink) and the pro-rata strategy (green) strategies with
enough vaccine to cover 10–50% of the population with one dose. Each row represents a dif-
ferent breakdown of VEDIS = 90% as a function of VESUS and VESYMP . Top row (A–C): VEDIS
is mediated by a reduction in symptoms upon infection. Middle row (D–F): VEDIS is mediated
by a combination of reduction in susceptibility to infection and reduction of symptoms upon
infection. Bottom row (G–I): VEDIS is mediated by a reduction in susceptibility to infection.
The columns correspond to assumptions that the single-dose efficacy (SDE) is low (left col-
umn, VEDIS1 = 18%), moderate (center column, VEDIS1 = 45%) or high (right column, VEDIS1
= 72%), corresponding 20, 50 or 80% of the 90% efficacy that is assumed following two doses
of vaccine, respectively. Shaded areas represent uncertainty intervals. Here, we assumed Reff =
1.1.
9
0 20 40 60 80 100 0 20 40 60 80 100 0 20 40 60 80 100

100
A
100
B
100
C
100
1 dose
2 doses
80 80 80 80
in each group
60 60 60 60
40 40 40 40
20 20 20 20
0 0 0 0
VESUS VESYMP VEI 0-19 20-49 50-64 65-74 75+ 0-19 20-49 50-64 65-74 75+ 0-19 20-49 50-64 65-74 75+
100
D
100
E
100
F
100
80 80 80 80
in each group
60 60 60 60
40 40 40 40
20 20 20 20
0 0 0 0
VESUS VESYMP VEI 0-19 20-49 50-64 65-74 75+ 0-19 20-49 50-64 65-74 75+ 0-19 20-49 50-64 65-74 75+
100
G
100
H
100
I
100
80 80 80 80
in each group
60 60 60 60
40 40 40 40
20 20 20 20
0 0 0 0
VESUS VESYMP VEI 0-19 20-49 50-64 65-74 75+ 0-19 20-49 50-64 65-74 75+ 0-19 20-49 50-64 65-74 75+
Figure S10: Optimal vaccine allocation to minimize deaths for different vaccine pro-
files with 50% coverage and assuming asymptomatic infections are 30% as infectious as
symptomatic infections. Optimal vaccine allocation for minimizing deaths for a vaccine with
VEDIS = 90% and assuming enough vaccine to cover 50% of the population with a single dose
(25% with two doses). For each panel (A-I), the bars represent the total percentage of the pop-
ulation in each vaccination group to be vaccinated, split in those receiving a single dose (light
blue) and those receiving two doses (dark blue). Each row represents a different breakdown of
VEDIS = 90% as a function of VESUS and VESYMP . Top row (A-C): VEDIS is mediated by a
reduction in symptoms upon infection. Middle row (D-F): VEDIS is mediated by a combination
of reduction in susceptibility to infection and reduction of symptoms upon infection. Bottom
row (G-I): VEDIS is mediated by a reduction in susceptibility to infection. The columns corre-
10
0 20 40 60 80 100 0 20 40 60 80 100 0 20 40 60 80 100

100
A100 B100 C100
80 80 80 80
Total infections
averted (%)
60 60 60 60
40 40 40 40
20 20 20 20
0 0 0 0
VESUSVESYMP VEI 10 20 30 40 50 10 20 30 40 50 10 20 30 40 50
100
D100 E100 F100
80 80 80 80
Total infections
averted (%)
60 60 60 60
40 40 40 40
20 20 20 20
0 0 0 0
VESUSVESYMP VEI 10 20 30 40 50 10 20 30 40 50 10 20 30 40 50
100
G100 H100 I 100
80 80 80 80
Total infections
averted (%)
60 60 60 60
40 40 40 40
Optimal
20 20 20 20 High-risk
Pro-rata
0 0 0 0
VESUSVESYMP VEI 10 20 30 40 50 10 20 30 40 50 10 20 30 40 50
Figure S11: Percentage of cumulative infections averted for different vaccine profiles as-
suming asymptomatic infections are 30% as infectious as symptomatic ones. Percentage of
cumulative infections averted for the optimal allocation strategy to minimize infections (blue),
the high-risk strategy (pink) and the pro-rata strategy (green) strategies with enough vaccine to
cover 10–50% of the population with one dose. Each row represents a different breakdown of
VEDIS = 90% as a function of VESUS and VESYMP . Top row (A–C): VEDIS is mediated by a
reduction in symptoms upon infection. Middle row (D–F): VEDIS is mediated by a combination
of reduction in susceptibility to infection and reduction of symptoms upon infection. Bottom
row (G–I): VEDIS is mediated by a reduction in susceptibility to infection. The columns corre-
Shaded areas represent uncertainty intervals. Here, we assumed Reff = 1.1.
11
0 20 40 60 80 100 0 20 40 60 80 100 0 20 40 60 80 100

100 100 100
1 dose
75 2 doses 75 75
50 50 50
10% coverage 25 25 25
0 0 0
100
D E
100
F
100
75 75 75
50 50 50
20% coverage 25 25 25
0 0 0
100
G H
100
I
100
75 75 75
50 50 50
30% coverage 25 25 25
0 0 0
100
J K
100
L
100
75 75 75
50 50 50
40% coverage 25 25 25
0 0 0
100
M N
100
O
100
75 75 75
50 50 50
50% coverage 25 25 25
0 0 0
0-19 20-49 50-64 65-74 75+ 0-19 20-49 50-64 65-74 75+ 0-19 20-49 50-64 65-74 75+
Figure S12: Optimal vaccine allocation strategies with different levels of coverage assum-
ing 10% of the population has pre-existing immunity. For each plot, the bars represent the
percentage of each age group vaccinated with a single dose (light blue) and two doses (dark
blue) when there is enough vaccine to cover 10% to 50% (as indicated by row) of the popula-
tion with a single dose. The columns correspond to assumptions that the single-dose efficacy
(SDE) is low (left column, VEDIS1 = 18%), moderate (center column, VEDIS1 = 45%) or high
(right column, VEDIS1 = 72%), corresponding 20, 50 or 80% of the 90% efficacy that is assumed
following two doses of vaccine, respectively. Here, we assumed Reff = 1.1.
12
0 20 40 60 80 100 0 20 40 60 80 100 0 20 40 60 80 100

A
100
B
100
C
100
1 dose
80 2 doses 80 80
(Prev =0.05%)
in each group
60 60 60
40 40 40
20 20 20
0 0 0
0-19 20-49 50-64 65-74 75+ 0-19 20-49 50-64 65-74 75+ 0-19 20-49 50-64 65-74 75+
D
100
E
100
F
100
80 80 80
in each group
(Prev =0.1%)
60 60 60
40 40 40
20 20 20
0 0 0
0-19 20-49 50-64 65-74 75+ 0-19 20-49 50-64 65-74 75+ 0-19 20-49 50-64 65-74 75+
G
100
H
100
I
100
80 80 80
in each group
(Prev =0.3%)
60 60 60
40 40 40
20 20 20
0 0 0
0-19 20-49 50-64 65-74 75+ 0-19 20-49 50-64 65-74 75+ 0-19 20-49 50-64 65-74 75+
Figure S13: Optimal vaccine allocation strategies to minimize deaths for different levels
of infection prevalence at the start of vaccination rollout. For each plot, the bars represent
the percentage of each age group vaccinated with a single dose (light blue) and two doses (dark
blue) when there is enough vaccine to cover 50% of the population with a single dose. Each
row represents starting the simulations assuming 0.05% (A-C), 0.1% (D-F) or 0.3% (G-I) of the
population is currently infected. The columns correspond to assumptions that the single-dose
or high (right column, VEDIS1 = 72%), corresponding 20, 50 or 80% of the 90% efficacy that is
assumed following two doses of vaccine, respectively. Here, we assumed Reff = 1.1.
13
0 20 40 60 80 100 0 20 40 60 80 100 0 20 40 60 80 100

A100 B100 C100
80 80 80
Deaths averted (%)
(Prev =0.05%)
60 60 60
40 40 40
20 20 20
0 0 0
10 20 30 40 50 10 20 30 40 50 10 20 30 40 50
D100 E100 F100
80 80 80
Deaths averted (%)
(Prev =0.1%)
60 60 60
40 40 40
20 20 20
0 0 0
10 20 30 40 50 10 20 30 40 50 10 20 30 40 50
G100 H100 I 100
Optimal
80 80 80 High-risk
Deaths averted (%)
Pro-rata
(Prev =0.3%)
60 60 60
40 40 40
20 20 20
0 0 0
10 20 30 40 50 10 20 30 40 50 10 20 30 40 50
Figure S14: Percentage of cumulative deaths averted for different infection prevalence at
the start of vaccination rollout. Percentage of cumulative deaths averted for the optimal allo-
cation strategy to minimize deaths (blue), the high-risk strategy (pink) and the pro-rata strategy
(green) strategies with enough vaccine to cover 10–50% of the population with one dose. Each
row represents starting the simulations assuming 0.05% (A-C), 0.1% (D-F) or 0.3% (G-I) of the
population is currently infected. The columns correspond to assumptions that the single-dose
or high (right column, VEDIS1 = 72%), corresponding 20, 50 or 80% of the 90% efficacy that
is assumed following two doses of vaccine, respectively. Shaded areas represent uncertainty
intervals. Here, we assumed Reff = 1.1.
14
0 20 40 60 80 100 0 20 40 60 80 100 0 20 40 60 80 100

100 VEDIS efficacy 100 VEDIS efficacy 100 VEDIS efficacy
1 dose
2 doses
10% coverage50 50 50
0 0 0
100 100 100
0 0 0
100 100 100
50 50 50
30% coverage
0 0 0
100 100 100
0 0 0
100 100 100
0 0 0
100 100 100
0 0 0
100 100 100
0 0 0
100 100 100
50 50 50
80% coverage
0 0 0
100 100 100
0 0 0
100 100 100
50 50 50
100% coverage
0 0 0
0-19 20-4950-6465-74 75+ 0-19 20-4950-6465-74 75+ 0-19 20-4950-6465-74 75+
Figure S15: Optimal vaccine allocation strategies to minimize deaths with different levels of cov-
erage with vaccination rollout (300K doses per week). For each plot, the bars represent the percentage
of each age group vaccinated with a single dose (light blue) and two doses (dark blue) when there is
enough vaccine to cover 10% to 100% (as indicated by row) of the population with a single dose. The
columns correspond to assumptions that the single-dose efficacy (SDE) is low (left column, VEDIS1 =
18%), moderate (center column, VEDIS1 = 45%) or high (right column, VEDIS1 = 72%), corresponding
20, 50 or 80% of the 90% efficacy that is assumed following two doses of vaccine, respectively. Here,
we assumed Reff = 1.1. 15
0 20 40 60 80 100 0 20 40 60 80 100 0 20 40 60 80 100

A B C
100 100 100
80 80 80
averted (%)
60 60 60
Deaths
40 40 40
Optimal
20 High-risk 20 20
Pro-rata
0 0 0
0 20 40 60 80 100 0 20 40 60 80 100 0 20 40 60 80 100
D E F
100 100 100
1 dose
80 2 doses 80 80
High-risk
Pro-rata
in each group
60 60 60
40 40 40
20 20 20
0 0 0
0-19 20-49 50-64 65-74 75+ 0-19 20-49 50-64 65-74 75+ 0-19 20-49 50-64 65-74 75+
G H I
Baseline
400 Optimal 400 400
Prevalence of infections
High-risk
300 Pro-rata 300 300
per 100,000
200 200 200
100 100 100
0 0 0
0 50 100 150 0 50 100 150 0 50 100 150
Days Days Days
Figure S16: Results with a faster vaccination rollout (300K doses per week). A–C. Per-
centage of deaths averted: Percentage of deaths averted for the optimal allocation strategy to
minimize deaths (blue), the high-risk strategy (pink) and the pro-rata strategy (green) strate-
gies with enough vaccine to cover 10–100% of the population with one dose (5–50% with two
doses), administering 300K doses per week. At this rate, 100% of the population can be vac-
cinated with a single dose in our time horizon. D–F. Allocation strategies: Optimal (light
and dark blue), high-risk (pink) and pro-rata (green) allocation strategies with enough vaccine
to cover 50% of the population with a single dose (25% with two doses). Within each panel,
the bars represent the percentage vaccinated in each vaccination group. G–I. Prevalence of
infections: Prevalence of active infections (per 100,000) in absence of vaccine (black), with
the optimal allocation strategy to minimize deaths (blue), the high-risk strategy (pink) or the
pro-rata strategy (green) with enough vaccine to cover 20% of the population with one dose
(10% with two doses). Shaded areas represent uncertainty intervals. The columns correspond
to assumptions that the single-dose efficacy (SDE) is low (left column, VEDIS1 = 18%), moder-
ate (center column, VEDIS1 = 45%) or high (right column, VEDIS1 = 72%), corresponding 20, 50
or 80% of the 90% efficacy that is assumed following two doses of vaccine, respectively. Here,
we assumed Reff = 1.1.
16
0 20 40 60 80 100 0 20 40 60 80 100 0 20 40 60 80 100

100 100 100
1 dose
75 2 doses 75 75
50 50 50
10% coverage 25 25 25
0 0 0
100
D E
100
F
100
75 75 75
50 50 50
20% coverage 25 25 25
0 0 0
100
G H
100
I
100
75 75 75
50 50 50
30% coverage 25 25 25
0 0 0
100
J K
100
L
100
75 75 75
50 50 50
40% coverage 25 25 25
0 0 0
100
M N
100
O
100
75 75 75
50 50 50
50% coverage 25 25 25
0 0 0
0-19 20-49 50-64 65-74 75+ 0-19 20-49 50-64 65-74 75+ 0-19 20-49 50-64 65-74 75+
Figure S17: Optimal vaccine allocation strategies to minimize deaths with different levels
of coverage with a vaccine reducing also infectiousness (VEI = 70%). For each plot, the
bars represent the percentage of each age group vaccinated with a single dose (light blue) and
two doses (dark blue) when there is enough vaccine to cover 10% (row A) to 50% (row E) of
the population with a single dose. Here, we assumed that the vaccine reduces susceptibility to
infection, symptoms given infection and infectiousness with VEI = 70%. The columns corre-
17
0 20 40 60 80 100 0 20 40 60 80 100 0 20 40 60 80 100

Deaths averted (%)
80 80 80
(Reff=1.1)
60 60 60
40 40 40
20 20 20
0 0 0
10 20 30 40 50 10 20 30 40 50 10 20 30 40 50
D100 E100 F100
Deaths averted (%)
80 80 80
(Reff=1.3)
60 60 60
40 40 40
20 20 20
0 0 0
10 20 30 40 50 10 20 30 40 50 10 20 30 40 50
G100 H100 I 100
Deaths averted (%)
80 80 80
(Reff=1.5)
60 60 60
40 40 40
20 20 20
0 0 0
10 20 30 40 50 10 20 30 40 50 10 20 30 40 50
J 100 K100 L100
Optimal
Deaths averted (%)
80 80 80 High-risk
(Reff=2.4)
60 60 60 Pro-rata
40 40 40
20 20 20
0 0 0
10 20 30 40 50 10 20 30 40 50 10 20 30 40 50
Figure S18: Percentage of deaths averted for different levels of SARS-CoV-2 transmission
with a vaccine reducing also infectiousness. Percentage of deaths averted for the optimal allo-
cation strategy to minimize deaths (blue), the high-risk strategy (pink) and the pro-rata strategy
(green) strategies with enough vaccine to cover 10-50% of the population with one dose. Each
row represents a different level of SARS-CoV-2 transmission resulting in Reff = 1.1 (A–C), 1.3
(D–F), 1.5 (G–I) or 2.4 (J–L). Here, we assumed that the vaccine reduces susceptibility to infec-
tion, symptoms given infection and infectiousness with VEI = 70%.The columns correspond to
80% of the 90% efficacy that is assumed following two doses of vaccine, respectively. Shaded
areas represent uncertainty intervals.
18
0 20 40 60 80 100 0 20 40 60 80 100 0 20 40 60 80 100

100 100 100
1 dose
75 2 doses 75 75
50 50 50
10% coverage 25 25 25
0 0 0
100
D E
100
F
100
75 75 75
50 50 50
20% coverage 25 25 25
0 0 0
100
G H
100
I
100
75 75 75
50 50 50
30% coverage 25 25 25
0 0 0
100
J K
100
L
100
75 75 75
50 50 50
40% coverage 25 25 25
0 0 0
100
M N
100
O
100
75 75 75
50 50 50
50% coverage 25 25 25
0 0 0
0-19 20-49 50-64 65-74 75+ 0-19 20-49 50-64 65-74 75+ 0-19 20-49 50-64 65-74 75+
Figure S19: Optimal vaccine allocation strategies to minimize deaths with different levels
of coverage assuming a different distribution of pre-existing immunity, similar to the dis-
tribution of cases observed in WA state as of February 2021 [24]. For each plot, the bars
represent the percentage of each age group vaccinated with a single dose (light blue) and two
doses (dark blue) when there is enough vaccine to cover 10% (row A) to 50% (row E) of the
population with a single dose. The columns correspond to assumptions that the single-dose
or high (right column, VEDIS1 = 72%), corresponding 20, 50 or 80% of the 90% efficacy that is
assumed following two doses of vaccine, respectively.
19
0 20 40 60 80 100 0 20 40 60 80 100 0 20 40 60 80 100

100 100 100
1 dose
75 2 doses 75 75
50 50 50
10% coverage 25 25 25
0 0 0
100
D E
100
F
100
75 75 75
50 50 50
20% coverage 25 25 25
0 0 0
100
G H
100
I
100
75 75 75
50 50 50
30% coverage 25 25 25
0 0 0
100
J K
100
L
100
75 75 75
50 50 50
40% coverage 25 25 25
0 0 0
100
M N
100
O
100
75 75 75
50 50 50
50% coverage 25 25 25
0 0 0
0-19 20-49 50-64 65-74 75+ 0-19 20-49 50-64 65-74 75+ 0-19 20-49 50-64 65-74 75+
Figure S20: Optimal vaccine allocation strategies to minimize deaths with different lev-
els of coverage assuming a different distribution of pre-existing immunity, similar to the
distribution of cases observed in two Indian States as of July 2020 [36]. For each plot, the
bars represent the percentage of each age group vaccinated with a single dose (light blue) and
two doses (dark blue) when there is enough vaccine to cover 10% (row A) to 50% (row E) of
the population with a single dose. Here, we assumed that the vaccine reduces susceptibility to
infection, symptoms given infection and infectiousness with VEI = 70%. The columns corre-
20
0 20 40 60 80 100 0 20 40 60 80 100 0 20 40 60 80 100

100 100 100
1 dose
75 2 doses 75 75
50 50 50
10% coverage 25 25 25
0 0 0
100
D E
100
F
100
75 75 75
50 50 50
20% coverage 25 25 25
0 0 0
100
G H
100
I
100
75 75 75
50 50 50
30% coverage 25 25 25
0 0 0
100
J K
100
L
100
75 75 75
50 50 50
40% coverage 25 25 25
0 0 0
100
M N
100
O
100
75 75 75
50 50 50
50% coverage 25 25 25
0 0 0
0-19 20-49 50-64 65-74 75+ 0-19 20-49 50-64 65-74 75+ 0-19 20-49 50-64 65-74 75+
Figure S21: Optimal vaccine allocation strategies to minimize deaths assuming increased
baseline transmission (R0 = 4). For each plot, the bars represent the percentage of each
age group vaccinated with a single dose (light blue) and two doses (dark blue) when there is
enough vaccine to cover 10% (row A) to 50% (row E) of the population with a single dose. The
columns correspond to assumptions that the single-dose efficacy (SDE) is low (left column,
VEDIS1 = 18%), moderate (center column, VEDIS1 = 45%) or high (right column, VEDIS1 =
72%), corresponding 20, 50 or 80% of the 90% efficacy that is assumed following two doses
of vaccine, respectively. Here, we assumed an increased baseline R0 = 4 and social distancing
interventions resulting in an Reff = 1.5.
21
0 20 40 60 80 100 0 20 40 60 80 100 0 20 40 60 80 100

Deaths averted (%)
80 80 80
(Reff=1.5)
60 60 60
40 40 40
20 20 20
0 0 0
10 20 30 40 50 10 20 30 40 50 10 20 30 40 50
D100 E100 F100
Deaths averted (%)
80 80 80
(Reff=1.7)
60 60 60
40 40 40
20 20 20
0 0 0
10 20 30 40 50 10 20 30 40 50 10 20 30 40 50
G100 H100 I 100
Deaths averted (%)
80 80 80
(Reff=2.0)
60 60 60
40 40 40
20 20 20
0 0 0
10 20 30 40 50 10 20 30 40 50 10 20 30 40 50
J 100 K100 L100
Optimal
Deaths averted (%)
80 80 80 High-risk
(Reff=3.2)
60 60 60 Pro-rata
40 40 40
20 20 20
0 0 0
10 20 30 40 50 10 20 30 40 50 10 20 30 40 50
assuming increased baseline transmission (R0 = 4). Percentage of deaths averted for the
optimal allocation strategy to minimize deaths (blue), the high-risk strategy (pink) and the pro-
rata strategy (green) strategies with enough vaccine to cover 10-50% of the population with
one dose. Here, we assumed that in absence of any social distancing intervention, the baseline
transmission is R0 = 4. Each row represents a different level of social distancing interventions
resulting in Reff = 1.5 (A–C), 1.7 (D–F), 2.0 (G–I) or 3.2 (J–L). The columns correspond to
80% of the 90% efficacy that is assumed following two doses of vaccine, respectively. Shaded
areas represent uncertainty intervals.
22
0 20 40 60 80 100 0 20 40 60 80 100 0 20 40 60 80 100

100 100 100
1 dose
75 2 doses 75 75
50 50 50
10% coverage 25 25 25
0 0 0
100
D E
100
F
100
75 75 75
50 50 50
20% coverage 25 25 25
0 0 0
100
G H
100
I
100
75 75 75
50 50 50
30% coverage 25 25 25
0 0 0
100
J K
100
L
100
75 75 75
50 50 50
40% coverage 25 25 25
0 0 0
100
M N
100
O
100
75 75 75
50 50 50
50% coverage 25 25 25
0 0 0
0-19 20-49 50-64 65-74 75+ 0-19 20-49 50-64 65-74 75+ 0-19 20-49 50-64 65-74 75+
Figure S23: Optimal vaccine allocation strategies to minimize deaths assuming a lower
vaccine efficacy. For each plot, the bars represent the percentage of each age group vaccinated
with a single dose (light blue) and two doses (dark blue) when there is enough vaccine to cover
10% (row A) to 50% (row E) of the population with a single dose. The columns correspond to
80% of the 90% efficacy that is assumed following two doses of vaccine, respectively. Here, we
assumed a lower vaccine efficacy, such that VEDIS = 72% after two doses.
23
0 20 40 60 80 100 0 20 40 60 80 100 0 20 40 60 80 100

Deaths averted (%)
80 80 80
(Reff=1.1)
60 60 60
40 40 40
20 20 20
0 0 0
10 20 30 40 50 10 20 30 40 50 10 20 30 40 50
D100 E100 F100
Deaths averted (%)
80 80 80
(Reff=1.3)
60 60 60
40 40 40
20 20 20
0 0 0
10 20 30 40 50 10 20 30 40 50 10 20 30 40 50
G100 H100 I 100
Deaths averted (%)
80 80 80
(Reff=1.5)
60 60 60
40 40 40
20 20 20
0 0 0
10 20 30 40 50 10 20 30 40 50 10 20 30 40 50
J 100 K100 L100
Optimal
Deaths averted (%)
80 80 80 High-risk
(Reff=2.4)
60 60 60 Pro-rata
40 40 40
20 20 20
0 0 0
10 20 30 40 50 10 20 30 40 50 10 20 30 40 50
assuming VEDIS = 72%. Percentage of deaths averted for the optimal allocation strategy to
minimize deaths (blue), the high-risk strategy (pink) and the pro-rata strategy (green) strategies
with enough vaccine to cover 10-50% of the population with one dose. Each row represents
a different level of social distancing interventions resulting in Reff = 1.5 (A–C), 1.7 (D–F), 2.0
(G–I) or 3.2 (J–L). The columns correspond to assumptions that the single-dose efficacy (SDE)
is low (left column, VEDIS1 = 14%), moderate (center column, VEDIS1 = 35%) or high (right
column, VEDIS1 = 58%), corresponding 20, 50 or 80% of the 90% efficacy that is assumed
following two doses of vaccine, respectively. Shaded areas represent uncertainty intervals.
24
TOTAL
0 25 50 75 100 0 25 50 75 100 0 25 50 75 100
VEDIS1 = 18% VEDIS1 = 45% VEDIS1 = 72% VEDIS = 90%
VESUS1 VESYMP1 VESUS1 VESYMP1 VESUS1 VESYMP1 VESUS VESYMP
100
80
60 Vaccine mediated
mainly by reducing
40 symptoms upon
0% 18% 0% 45% 0% 72% 0% 90%
h! 20 infection
0
VESUS VESYMP
100
80 Vaccine mediated
by reducing
60 symptoms upon
40 infection and 9% 10% 26% 26% 50% 44% 70% 66%
20 reducing
susceptibility to
0 infection
VESUS VESYMP
100
80
60 Vaccine mediated
mainly by reducing
40 susceptibility to
18% 0% 45% 0% 72% 0% 90% 0%
20 infection
0
VESUS VESYMP
Table S1: Description of vaccine efficacies used in the model.
Supplemental Tables
25
Parameter Meaning Value (Range) Reference

1/γE mean duration of latent period 3 (1.5–4.5) d [69, 70]
1/γP mean pre-symptomatic period 2 (1–3) d [71]
1/γA mean infectious period of asymptomatic infec- 6 (3–8) d assumeda
tions
1/γI mean infectious period of symptomatic infec- 4 (2–5) d [72, 73]
tions not requiring hospitalization after develop-
ing symptoms
1/γH mean duration of non-ICU hospitalization age-stratified [22]
1/γC mean duration of ICU hospitalization age-stratified [22]
k0−14 proportion of infections that are symptomatic 0.25 (0.4–0.8) [74]
k15+ proportion of infections that are symptomatic 0.60 (0.4–0.8) [22, 75, 76]
h proportion of symptomatic infections requiring age-stratified [56]
hospitalization
c proportion of hospitalizations requiring ICU age-stratified [56]
d proportion of all hospitalizations resulting in age-stratified [57]
death
rA relative infectiousness of asymptomatic infec- 0.75 (0.3) [22]
tions b
rH relative infectiousness of hospitalized infections 0 assumed
rP relative infectiousness of pre-symptomatic infec- 1 (0.7–1.3) [77]
tionsc
m0−14 relative susceptibility for those aged 0–14 0.56 [74, 70]
m15−64 relative susceptibility for those aged 15–64 1 [74, 70]
m65+ relative susceptibility for those age 65+ 2.7 [78]
σ mean time from symptom onset to hospitaliza- 3.8 d [79]
tion
R0 basic reproductive number 3 [80, 81]
Reff effective reproductive number at the beginning of 1.1, 1.3, 1.5, 2.4 assumedd
vaccination
β transmission coefficient calculated −
M contact matrix − [21]
N total population 7,615,000 [82]
R(0) proportion of the population immune at t = 0 0.2 (0.1) [23]
I(0) infected proportion of the total population at t = 0.001 (0.0005 and [24]
0 0.003)
a
assumed to match the duration of infectiousness of symptomatic infections
b
with respect to symptomatic not hospitalized infections
c
with respect to symptomatic not hospitalized infections
d
see table S3 for details.
Table S2: Description of parameters used in the model.
26
Reff Home Work Other locations School

1.1 1 0.6 0.2 0.1
1.3 1 0.6 0.4 0.1
1.5 1 0.6 0.5 0.5
2.4 1 1 1 1
Table S3: Multipliers used based on the contact matrices given in Prem et al. [21].
27
Mathematical model
Transmission model:
We built upon our previous model of SARS-CoV-2 transmission and vaccination with 16 age
groups: 0–4, 5–9, 10–14, 15–19, 20–24, 25–29, 30–34, 35–39, 40–44, 45–49, 50–54, 55–59,
60–64, 65–69, 70–74, and 75+ [20]. We used the population of Washington state (7.6 million
people, [82]) and US demographics [83]. For each age group i, our model tracks susceptible
Si , exposed Ei , asymptomatic Ai , pre-symptomatic Pi and symptomatic infected individuals
classed by disease severity (assumed to be equally infectious). Symptomatic individuals have
one of three fates: they become mildly symptomatic Ii , hospitalized in a non-ICU ward Hi , or
hospitalized requiring intensive care, ICUi . After infection, individuals move to the respec-
tive recovered classes: recovered asymptomatic, mildly symptomatic, non-ICU hospitalized
and ICU hospitalized (denoted by RAi , Ri , RHi and RCi respectively). Individuals may re-
ceive one or two doses of vaccine (analagous compartments indexed by j = 1, 2 respectively)
(Fig. S1 and Vaccination section below). We assumed that asymptomatic are less infectious
than symptomatic (not hospitalized) infections but confer equal immunity. Further, we assumed
that both naturally-induced and vaccine-induced immunity are long lasting, so that there is no
waning during the time period analyzed.

We used a previously published age-structured contact matrix M for contact patterns in the
US [21] and corrected for reciprocity. We assumed a baseline R0 = 3 in the absence of any
social distancing interventions. We also considered an alternative scenario resulting in increased
transmission due to the co-circulation of the original and new variants that would result in a
baseline R0 = 4. To simulate social distancing interventions, we modified the matrices given

in [21] (matrices corresponding to contacts at “home”, “work”, “other locations” and “school”)
according to table S3 and Fig. S2 to obtain an effective reproduction number Reff = 1.1, 1.3, 1.5,
28
or 2.4 (assuming 20% pre-existing immunity). We informed these parameter choices by the
different social distancing interventions that have been enacted in WA state over the course of
the pandemic and by mobility data [84, 85, 86, 87, 88, 89]. We used estimated age-specific
proportions of infections that require hospitalization and critical care from [56]. Estimated
proportions of hospitalizations that result in death were taken from [57]. These reports have
different age brackets than those in our model, so we combined the brackets according to the
proportion of the population in each bracket (e.g., for the oldest group in our model, ≥ 75,
we weighted the rates in [56] by the relative percentages of the US population aged 75–80 and
≥ 80). Hospitalized individuals are assumed no longer infectious. Table S2 summarizes the
parameter values, ranges, and sources for the model.
Simulations were run with initial conditions set to a 20% of the population with pre-existing
immunity, distributed proportionally to population size (pro-rata) and disease severity, respec-
tively (additional scenario, 10%, see Sensitivity Analysis). In addition, simulations were run
with 7,615 infections (equivalent to 0.1% of the total population) initially, distributed among
the infectious symptomatic and asymptomatic infectious compartments ( Aij , AV,ij , Iij , IV,ij ,
Hij , HV,ij , Cij and CV,ij ). We ran additional scenarios with an initial prevalence of 0.05% and
0.3% of the total population.
Vaccination
Following the ideas of Halloran et al. [28], we assumed a leaky vaccine (that is, a vaccine that
confers partial protection to all the vaccinees) that can have three effects on the vaccinated indi-
viduals. First, the vaccine can reduce the probability of acquiring a SARS-CoV-2 infection, (we
denote this effect by VESUS ). Second, the vaccine can also potentially reduce the probability of
developing COVID-19 symptoms upon infection (referred to as VESYMP ), or third, reduce the
infectiousness of vaccinated individuals (referred to as VEI ), Fig. S3B. There is a multiplica-
29
tive relationship between the vaccine efficacy against laboratory-confirmed COVID-19 disease,
VEDIS , VESUS and VESYMP [90], so that
VEDIS = 1 − (1 − VESUS )(1 − VESYMP ).
A vaccine highly efficacious against disease could be either mediated mainly by protecting
vaccinated individuals against infection (high VESUS ), or mainly by preventing them from de-
veloping symptoms once infected (high VESYMP ), or a combination of both. A vaccine with
a high VESUS or a high VEI (irrespective of VESYMP ) would have a bigger effect on the trans-
mission dynamics of SARS-CoV-2, resulting in a greater population impact than one mediated
primarily by VESYMP . In fact, a vaccine mediated exclusively by VESYMP might have only
a direct effect, protecting only those vaccinated (this would be the case if asymptomatic and
symptomatic individuals are equally infectious). We denote by VESUS1 , VESYMP1 and VEI1 the
single-dose vaccine efficacies for susceptibility, symptomatic infection upon infection, and in-
fectiousness upon infection respectively. Values for all the combinations of vaccine efficacy
profiles considered can be found in Table S1.
The equations for this model are given by
30
Unvaccinated:
dSi
= −mi λSi ,
dt
dEi
= mi λSi − γE Ei ,
dt
dAi
= (1 − ki )γE Ei − γA Ai ,
dt
dPi
= ki γE Ei − γP Pi ,
dt
dIi
= γP Pi − (1 − h)γI Ii − h(1 − c)σIi − hcσIi ,
dt
dHi
= h(1 − c)σIi − γH Hi ,
dt
dICU i
= hcσIi − γC ICUi ,
dt
dRAi
= γ A Ai ,
dt
dRi
= γI Ii ,
dt
dRH i
= γH Hi ,
dt
dRC i
= γC ICUi ,
dt
31
Vaccinated (j = 1, 2 denotes vaccination with one or two doses respectively):
dSij
= −(1 − VESUSj )mi λSij ,
dt
dEij
= (1 − VESUSj )mi λSij − γE Eij ,
dt
dAij
= 1 − ki (1 − VESYMPj ) γE Eij − γA Aij ,
dt
dPij
= ki (1 − VESYMPj )γE Eij − γP Pij ,
dt
dIij
= γP Pij − (1 − h)γI Iij − h(1 − c)σIij − hcσIij ,
dt
dHij
= h(1 − c)σIij − γH Hij ,
dt
dICU ij
= hcσIij − γC ICUij ,
dt
dRAij
= γA Aij ,
dt
dRij
= γI Iij ,
dt
dRH ij
= γH Hij ,
dt
dRC ij
= γC ICUij ,
dt
where λ is the force of infection given by

16
X Mh i
λ=β rA (Ak + ψ1 Ak1 + ψ2 Ak2 ) + rP (Pk + ψ1 Pk1 + ψ2 Pk2 ) + (Ik + ψ1 Ik1 + ψ2 Ik2 ) ,
k=1
Nk
with ψ1 = 1 − VEI1 , ψ2 = 1 − VEI , and M is the sum of the contact matrices given in [21],
corrected for reciprocity and weighted by the multipliers given in table S3.
Modeling vaccination campaigns
Vaccination campaigns were modeled assuming 150,000 doses of vaccines delivered weekly,
over the span of ∼6 months (28 weeks). At this rate, 50% of the population can be vaccinated
over this time period with a single dose (25% with two doses). We also analyzed an alterna-
tive scenario with 300,000 doses delivered weekly (corresponding to vaccinating 100% of the
32
population with one dose over the same time period).

For each vaccination coverage and strategy considered, we computed within each age-group
the fraction of susceptible individuals among all those individuals in that group who could have
sought the vaccine (susceptible, exposed, infected pre-symptomatic, infected asymptomatic,
and recovered asymptomatic populations), and used that fraction as the fraction of people who
were actually vaccinated in each age-group, while assuming that the remaining vaccine would
be wasted. Because it is expected that vaccine supplies will ramp up considerably over the
second half of 2021 and into 2022, we focused on the first few months of vaccine availability
and set 6 months as our time horizon, both for the optimization and for the population impact.
We implemented the vaccination campaigns following current implementation in the US,
that is, vaccinating individuals starting always with the oldest age-group and moving sequen-
tially in decreasing order across the vaccine groups. For vaccination strategies that included
vaccination with one and two doses of vaccine, we vaccinated first all the age-groups receiving
two doses and then those receiving one dose. For example, if a particular strategy allocates
vaccine as follows: 10% of adults aged 20–50 vaccinated with one dose, 10% of adults aged
50–65 vaccinated with two doses, 15% of adults aged 65–75 vaccinated with one dose and 40%
of adults aged 75 and older vaccinated with two doses, then the vaccination in our model goes
as follows: 1) vaccinate 40% of adults aged 75 and older with one dose for as many weeks as
necessary, then repeat this to vaccinate them with their second dose. 2) Then we will vaccinate
10% of the adults aged 50–65 with two doses (similarly to the previous steps, in two rounds). 3)
Then we will vaccinate 15% of adults aged 65–75 with one dose and finally 4) we will vaccinate
10% of those aged 20–50 with a single dose.
We chose this implementation because it closely reflects the current implementations around
the world, with interest to minimize death. However, it is important to bear in mind the potential
artifacts of this implementation. First, this implementation tends to favor the high-risk strategy
33
but it might disadvantage other strategies, in particular the pro-rata strategy . Second, this
implementation works well to minimize deaths but might not ideal to minimize infections, since
the groups driving the epidemic (adults aged 20–49 and children) are the last to be vaccinated.
Furthermore, due to this implementation, a particular allocation can, in principle, avert fewer
infections or deaths than do allocations with less coverage. This is because in our model, as
more vaccine is available, it is always distributed to older adults first. More coverage implies
more time spent vaccinating the older adults vaccination groups, who transmit the least, hence
delaying vaccination to the younger age groups, who are those transmitting most. This was
apparent for the pro-rata strategy when minimizing infections.
Optimization
Objective functions: We performed the optimization routine to minimize five different objec-
tive functions: cumulative number of infections, cumulative number of symptomatic infections,
cumulative number of deaths, maximum number of hospitalizations not requiring intensive care,
and maximum number of hospitalizations requiring intensive care. For each of these, we ran
the deterministic model for 6 months (our time horizon).
Optimization: Here we describe our optimization routine, adapted from our previous work
[20]. We randomly selected 10,000 points on a coarse grid [91] of the unit simplex in the
vaccination group space (the set of vectors (v1 , v2 , . . . , v5 ) with non-negative entries such that
P5
i=1 vi = 1). The grid was chosen so that the unit simplex was divided into 0.05 units and
was computed in Sage [92]. For each point in the coarse grid, the five objective functions were
evaluated. For each of these objective functions, we selected the best 25 decision variables
obtained in the grid search, the pro-rata allocation vector, the high-risk allocation vector and an
additional 25 decision variables sampled uniformly from the unit simplex [93], and used these
34
52 points as initial points for the Nelder-Mead minimizer implemented in SciPy [94, 95]. Full
details of the optimization routine can be found in [20].
The optimization for each combination of parameters (vaccination coverage, values of dif-
ferent vaccine profiles, level of viral transmission, etc.) was run independently. This, together
with the way vaccination campaigns was implemented (for the reasons explained above), can
result in the optimal allocation strategies that are not always monotonic functions of coverage.
We used a heuristic method because it is fast, and using a method that returns a guarantee
of optimality is very difficult for complex black-box objective functions. We took a very large
sample of the entire feasible set to ensure a thorough search to increase the chance that our
solution is nearly globally optimal. Furthermore, the sensitivity analysis shows that the optimal
solutions we found are robust to changes in parameters and, even though we cannot guarantee
they are globally optimal, our solutions either coincide with or outperform the pro-rata and
high-risk strategies, so they are relatively optimal in that sense.
Uncertainty analysis
We examined the uncertainty in the output measures (percentage of infections averted and per-
centage of deaths averted, etc.) arising from uncertainty surrounding the model parameters.
The following model parameters were varied for this analysis: the duration of the latent period,
the duration of the pre-symptomatic, symptomatic and asymptomatic infectious periods, the
relative infectiousness of the pre-symptomatic infected individuals, and the proportion of infec-
tions that are asymptomatic. We sampled parameter sets from predetermined distributions as
follows: for the duration of the latent period, the duration of the pre-symptomatic, symptomatic
and asymptomatic infectious periods we sampled gamma distributions with means given in ta-
ble S2. For the proportion of asymptomatic infections and the relative infectiousness of the
pre-symptomatic individuals we used truncated normal distributions with means and ranges
35
given in table S2. We then sampled 1000 parameter sets and evaluated all three strategies (op-
timal, pro-rata and high-risk) for each of those sets. We also ran the simulation in absence of
vaccination. We then computed the outcomes of interest and removed the the top and bottom
2.5%. The shaded areas presented in the figures are the result of this analysis.
36

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medRxiv preprint doi: https://doi.org/10.1101/2020.12.31.20249099; this version posted April 15, 2021.

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Optimizing vaccine allocation for COVID-19

health of those populations as well as that of the global population [9].

In this work, we addressed two questions of public-health importance: 1. Who should be

asymptomatic infections are 75% as infectious as symptomatic infections (alternative scenario:

We considered a baseline R0 = 3 (alternative scenario R0 = 4, Sensitivity Analysis) with

burden: cumulative infections, cumulative symptomatic infections, cumulative deaths, maxi-

for result interpretation.

Modeling the vaccine effects

COVID-19, or the multiplicative reduction in per-exposure risk of disease which we denote by

probability of acquiring a SARS-CoV-2 infection (measured by VESUS ), reduce the probabil-

infectiousness of vaccinated individuals upon infection (measured by VEI , Fig. S3A).

vaccination in the inter-vaccination period.

Modeling vaccination campaigns

given in the SM).

(Uncertainty analysis, SM).

Results assuming low background viral transmission.

in a significant reduction in overall transmission and hospitalizations (Figs. 2 and S5). As

UI: 60–70) vs. pro-rata: 22% (95% UI:17–25)), Fig. 3D.

Results assuming moderate or high background viral transmission.

minimize deaths reduced transmission (Fig. 4G–L).

Different metrics have different optimal allocation strategies.

pandemic, and minimizing each produced a different optimal allocation strategy.

When minimizing outcomes affecting transmission (total infections or total symptomatic

The vaccine profile shapes the optimal allocation strategy.

mortality if exclusively mediated by preventing infection (Fig. 10C and I).

age), Fig. S9I.

by reducing symptoms or if it was mediated by a combination of reducing symptoms and pre-

scenario, Figs. S9C) and S11C.

Results assuming 10% pre-existing immunity at the start of vaccination:

Results assuming lower or higher infection prevalence at the beginning of

Results assuming more rapid vaccine delivery:

the vaccine had a high SDE (Fig. S16G–I).

Results assuming vaccine efficacy in reducing infectiousness upon infec-

Results assuming a different distribution of pre-existing immunity:

In this section we investigated the effect of different distributions of pre-existing immunity on

Results assuming increased transmission due to establishment of new vari-

We repeated our main analysis assuming a baseline R0 = 4, representing an overall increase

of social distancing interventions considered (assuming 20% pre-existing immunity) resulted in

Results assuming a lower vaccine efficacy.

UI:59–68) vs. 74% (95% UI:68–77)), Figs. 3 and S24.

of vaccine to provide full protection. In contrast, however, when SARS-CoV-2 transmission is

incorporate in the metrics of disease burden in future work.

We quantified the advantages and disadvantages of two vaccination prioritization schedules

then important to determine country-based estimates of these rates to adequately parameterize

rise rapidly in frequency [66].

receiving vaccination under population campaigns—especially among those receiving a single

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