Comment
CoronaVac: more data for regulators and policy makers
As of July, 2021, almost 3 billion doses of COVID-19
vaccines have been administered globally.1 However,
there remains an urgent need to broaden access to safe
and effective COVID-19 vaccines, especially in low-income
and middle-income countries experiencing surges in
SARS-CoV-2 infections. Inactivated viral vaccines are an
established technology and have several advantages for
large-scale roll-out, including their stability at normal
refrigeration temperatures and their long shelf-life.2
Several inactivated SARS-CoV-2 candidate vaccines are in
phase 3/4 trials, and two have received WHO emergency
use authorisation: CoronaVac (developed by Sinovac Life
Sciences, Beijing, China) and BBIBP-CorV (Sinopharm,
Beijing, China).3
In The Lancet, Mine Durusu Tanriover and colleagues4
present the interim results of a double-blind, randomised,
controlled trial of CoronaVac versus placebo in Turkey.
Adults aged 18–59 years who were seronegative and
RT-PCR-negative for SARS-CoV-2 infection received
two doses of CoronaVac (3 μg β-propiolactone-
inactivated SARS-CoV-2 in 0·5 mL aqueous suspension
with 0·45 mg/mL aluminium) or placebo (containing
all the ingredients except the inactivated virus) with a
14-day interval between doses. The intention-to-treat
population (n=10 214) consisted of 5907 (57·8%) men,
4307 (42·2%) women, 3675 (36·0%) health-care workers,
and 1463 (15·6%) participants with a body-mass index of
greater than or equal to 30 kg/m², with an overall median
age of 45 years (IQR 37–51).
The primary, per protocol analysis of vaccine efficacy
included 10 029 participants who received two doses
of vaccine (n=6559) or placebo (n=3470). The primary
outcome was the incidence rate of PCR-confirmed
symptomatic COVID-19 occurring later than 14 days after
the second dose, of which 41 cases were reported. Nine of
these cases were in the CoronaVac group (incidence rate
31·7 cases [95% CI 14·6–59·3] per 1000 person-years) and
32 were in the placebo group (192·3 cases [135·7–261·1]
per 1000 person-years), giving a vaccine efficacy of 83·5%
(95% CI 65·4–92·1; p<0·0001). Six participants were
hospitalised with COVID-19, all in the placebo group.
Adverse events (analysed in the intention-to-treat
population) were reported in 1259 (18·9%) CoronaVac
recipients and 603 (16·9%) placebo recipients. Injection
site pain and fatigue were the most commonly reported
www.thelancet.com Published online July 8, 2021 https://doi.org/10.1016/S0140-6736(21)01543-9 1
local and systemic adverse events, respectively, and Published Online
July 8, 2021
both were more common in the vaccine group and https://doi.org/10.1016/
were mostly of grade 2 severity or less. 11 participants S0140-6736(21)01543-9
(six [0·1%] in the vaccine group and five [0·1%] in the See Online/Articles
https://doi.org/10.1016/
placebo group) had serious adverse events, of which one S0140-6736(21)01429-X
event (a severe allergic reaction) was judged to be related
to the vaccine.
Immunogenicity analyses were done in a subset of
participants (n=1413) at 14 days after the second dose.
Seroconversion was measured with use of a commercial
ELISA-based assay to detect IgG and IgM antibodies
specific for the receptor-binding domain (RBD) of
the SARS-CoV-2 spike protein, and was observed in
880 (89·7%) of 981 vaccine recipients and 19 (4·4%) of
432 placebo recipients (with seropositivity in the placebo
group presumed to be due to SARS-CoV-2 infection).
An in-house, live virus neutralisation assay showed that
356 (92·0%) of 387 seropositive participants had also
developed detectable levels of neutralising antibodies
(mean antibody titres of ≥1/15).
Tanriover and colleagues’ findings suggest that two
doses of CoronaVac have robust efficacy (within the
WHO target product profile for SARS-CoV-2 vaccines)5
and acceptable tolerability when administered with a
14-day interval. CoronaVac is also available as single-
dose vials, which improves ease of administration and
reduces wastage.
Strengths of the study include the large sample, robust
mechanisms of capturing symptomatic COVID-19
Chris McGrath/Staff/Getty Images
 Comment
outcomes using weekly automated telephone
questionnaires, and the double-blind design. One
limitation of the study was the early censoring of the
efficacy analysis due to the emergency use authorisation
of the vaccine in Turkey, granted as a result of rising
local case numbers. In addition, the median follow-
up period was short, at only 43 days (IQR 36–48).
Participants in the study were relatively young and had
few comorbidities, limiting the ability to infer vaccine
efficacy in people more susceptible to severe COVID-19.
However, previous published data suggest that immune
responses elicited by CoronaVac are similar in adults
aged 18–59 years and 60 years and older.6
No viral sequencing data were presented and, although
it can be assumed that a proportion of the cases in the
study timeframe (September, 2020, to January, 2021)
were caused by SARS-CoV-2 lineage B.1.1.7 (the alpha
variant of concern), no conclusions can be drawn about
the efficacy of CoronaVac against different SARS-CoV-2
lineages. Notably, the preliminary results of the CoronaVac
phase 3 trial in Brazil showed vaccine efficacy of 50·7%
(95% CI 35·9 to 62·0%) against symptomatic disease
when SARS-CoV-2 lineage P.2 (the zeta variant) was the
predominant circulating lineage,7 and a test-negative
case-control study done during a period of SARS-CoV-2
lineage P.1 (gamma variant) dominance estimated
vaccine effectiveness at 36·8% (–54·9 to 74·2).8
The anti-RBD antibody results presented by Tanriover
and colleagues4 were non-quantitative. Although an
immune correlate of protection for COVID-19 remains
to be determined, absolute antibody titres at multiple
timepoints alongside a benchmark of convalescent
serum or WHO serum standard would have allowed
the comparison of immunogenicity with other vaccine
candidates. A phase 1/2 study of CoronaVac9 showed
lower antibody titres after a single dose than after
two doses, which could explain the low efficacy of 46·4%
(95% CI 0·4–71·2) observed 14–27 days after the first dose
of vaccine in the current study. These data reinforce the
need for two doses of CoronaVac for adequate protection.
During the COVID-19 pandemic, clinical trials have
been done at pace with rolling regulatory reviews as
manufacturers strive to produce safe and effective
vaccines. Competent authorities face the dilemma
between waiting for phase 3 efficacy data to support
regulatory approval and the urgent need to vaccinate
vulnerable populations, as occurred in Turkey during
2 www.thelancet.com Published online July 8, 2021 https://doi.org/10.1016/S0140-6736(21)01543-9
this trial. Reduction in disease prevalence through
vaccine deployment coupled with non-pharmacological
interventions can itself impair the assessment of vaccine
efficacy. China is reported to have approved CoronaVac
for vaccination of high-risk groups in June, 2020,9 after
phase 1/2 data showed that the vaccine was well tolerated
and immunogenic;10 however, few local effectiveness data
are available because of the low incidence of COVID-19.11
Countries with a high incidence of disease, including
Indonesia, Brazil, and Chile, authorised CoronaVac for
emergency use in early 2021 and have subsequently
generated interim efficacy data from phase 3 trials7,8 as
well as post-authorisation passive safety surveillance data,
which have contributed to the WHO authorisation.12 Peer-
reviewed publication of phase 3 results such as these are
vital to strengthen public confidence and inform policy
decisions on the introduction and use of novel vaccines.
As countries open their economies and restart
international travel, digital proof of vaccination and
mutual recognition of vaccines will become increasingly
important. Open access to data on vaccines yet to be
adopted locally will help to inform countries on whether
to accept travellers who have received these vaccines.13,14
The recent WHO recommendation for use of
CoronaVac,3 which is currently approved in 32 countries,
could also facilitate free, safe movement of vaccinated
individuals.
Tanriover and colleagues’ study4 suggests that
CoronaVac is another useful tool in the global fight
against COVID-19, although more data are needed
on its efficacy against emerging SARS-CoV-2 variants
and on its duration of protection across different age
groups and geographical settings and in the presence
of comorbidities. The results of ongoing effectiveness
studies (NCT04747821 and NCT04789356) and immu­
nogenicity studies (NCT04756830 and NCT04775069)
are keenly awaited.
MNR is a principal investigator on the AstraZeneca COVID-19 vaccine trials at
the Oxford Vaccine Group but does not receive any personal fees or grants from
any pharmaceutical companies. LJJ is the director of public health for the
National Immunisation Office in the Health Service Executive, Dublin, Ireland,
and is responsible for the coordination of national immunisation programmes.
The views expressed are those of the authors and do not necessarily represent
the views of the University of Oxford or the Health Service Executive.
*Maheshi N Ramasamy, Lucy J Jessop
maheshi.ramasamy@paediatrics.ox.ac.uk
Oxford Vaccine Group, Department of Paediatrics and Centre for Clinical
Vaccinology and Tropical Medicine, University of Oxford, Oxford OX3 7LE, UK
(MNR); Oxford University Hospitals NHS Foundation Trust, Oxford, UK (MNR);
National Immunisation Office, Health Service Executive, Dublin, Ireland (LJJ)

1 WHO. WHO coronavirus (COVID-19) dashboard. July 6, 2021. https://covid19.
who.int (accessed July 7, 2021).
2 Plotkin S, Orenstein W, Offit P. Vaccines, 5th edn. Philadelphia, PA:
Saunders/Elsevier, 2008.
3 WHO. Status of COVID-19 vaccines within WHO EUL/PQ evaluation
process. June 16, 2021. https://extranet.who.int/pqweb/sites/default/files/
documents/Status_of_COVID-19_Vaccines_within_WHO_EUL-PQ_
evaluation_process-16June2021_Final.pdf (accessed June 20, 2021).
4 Tanriover MD, Doğanay HL, Akova M, et al. Efficacy and safety of an
inactivated whole-virion SARS-CoV-2 vaccine (CoronaVac): interim results
of a double-blind, randomised, placebo-controlled, phase 3 trial in Turkey.
Lancet 2021; published online July 8. https://doi.org/10.1016/
S0140-6736(21)01429-X.
5 WHO. WHO target product profiles for COVID-19 vaccines: version 3.
Geneva: World Health Organisation, 2020. https://www.who.int/
publications/m/item/who-target-product-profiles-for-covid-19-vaccines
(accessed June 19, 2021).
6 Wu Z, Hu Y, Xu M, et al. Safety, tolerability, and immunogenicity of an
inactivated SARS-CoV-2 vaccine (CoronaVac) in healthy adults aged
60 years and older: a randomised, double-blind, placebo-controlled,
phase 1/2 clinical trial. Lancet Infect Dis 2021; 21: 803–12.
7 Palacios R, Batista AP, Albuquerque CSN, et al. Efficacy and safety of a
COVID-19 inactivated vaccine in healthcare professionals in Brazil:
the PROFISCOV study. SSRN 2021; published online April 14. http://dx.doi.
org/10.2139/ssrn.3822780 (preprint).
8 Hitchings MD, Ranzani OT, Scaramuzzini Torres MS, et al. Effectiveness of
CoronaVac among healthcare workers in the setting of high SARS-CoV-2
Gamma variant transmission in Manaus, Brazil: a test-negative case-
control study. medRxiv 2021; published online May 1. https://doi.org/
10.1101/2021.04.07.21255081 (preprint).
www.thelancet.com Published online July 8, 2021 https://doi.org/10.1016/S0140-6736(21)01543-9 3
Comment
9 Reuters Staff. Sinovac’s coronavirus vaccine candidate approved for
emergency use in China –source. Reuters, Aug 28, 2020. https://www.reuters.
com/article/us-health-coronavirus-china-vaccines-idUSKBN25O0Z3
(accessed June 24, 2021).
10 Zhang Y, Zeng G, Pan H, et al. Safety, tolerability, and immunogenicity of an
inactivated SARS-CoV-2 vaccine in healthy adults aged 18–59 years:
a randomised, double-blind, placebo-controlled, phase 1/2 clinical trial.
Lancet Infect Dis 2021; 21: 181–92.
11 WHO. WHO coronavirus (COVID-19) dashboard—China situation.
June 24, 2021. https://covid19.who.int/region/wpro/country/cn (accessed
June 24, 2021).
12 WHO, SAGE Working Group on COVID-19 vaccines. Background document
on the inactivated vaccine Sinovac-CoronaVac against COVID-19.
May 24, 2021. https://www.who.int/publications/i/item/WHO-2019-nCoV-
vaccines-SAGE_recommendation-Sinovac-CoronaVac-background-2021.1
(accessed June 24, 2021).
13 European Commission. EU digital COVID certificate factsheet. 2021.
https://ec.europa.eu/info/live-work-travel-eu/coronavirus-response/safe-
covid-19-vaccines-europeans/eu-digital-covid-certificate_en (accessed
June 20, 2021).
14 European Medicines Agency. COVID-19 vaccines: authorised. June 18, 2021.
https://www.ema.europa.eu/en/human-regulatory/overview/public-
health-threats/coronavirus-disease-covid-19/treatments-vaccines/
vaccines-covid-19/covid-19-vaccines-authorised#safety-updates-for-
authorised-covid-19-vaccines-section (accessed June 20, 2021).