Efektifkah

Vaksin
Terhadap
Varian Baru
AMIN SOEBANDRIO
LEMBAGA EIJKMAN

3/28/2021 1
 Know You Enemy

Clinical Microbiology Review. October 2020 Volume 33 Issue 4 e00028-20

cmr.asm.org
3/28/202110 2
Downloaded from http://cmr.asm.org/ on June 24, 2020 at UNIVERSITY OF
Know your enemy

Jain S et al. Vaccines 2020, 8, 649

3/28/2021 3
 Host Defence

3/28/2021 4
Front. Pharmacol., 19 June 2020 | https://doi.org/10.3389/fphar.2020.00937
 Why we use vaccines
Vaccines can prevent infectious
diseases. When most people in a community
are vaccinated against a disease, the
• Examples of vaccine-preventable ability of the pathogen to spread is
diseases are: measles, polio, limited. This is called ‘herd’ or
hepatitis B, influenza and many ‘indirect’ or ‘population’ immunity.
others.

When many people have immunity, this

also indirectly protects people who cannot
be vaccinated, such as very young babies
and those who have compromised
immune systems.

WHO: CORONAVIRUS UPDATE 37. LAST UPDATE: 06

3/28/2021 October2020 5
 Vaccine Platforms
https://vaccinemapper.nd.edu/vaccine-design/ Accessed 28/03/2021
Nature Materials | VOL 19 | August 2020 | 810–820
3/28/2021 6
 How
Vaccine
Platforms
Work

https://www.pharmaceutical-journal.com/news-and-analysis/infographics/the-
race-to-stop-covid-19/20207792.article?firstPass=false
3/28/2021 7
Immune
Response to • Jain S et al. Vaccines 2020, 8, 649

Vaccines
3/28/2021 8
 Virus
Mutation
➢Random process
➢Path for the most
adaptive to survival
➢Structural and non-
structural
➢Not always beneficial

Mc Garty TP. Technical Report · January 2021 DOI: 10.13140/RG.2.2.15011.68644

3/28/2021 9
Tiga proses mutasi Virus Corona
1. Mutasi muncul secara intrinsik sebagai kesalahan penyalinan
selama replikasi virus, suatu proses yang dapat dikurangi dalam
SARS-CoV-2 relatif terhadap virus RNA lainnya, karena fakta
bahwa polimerase virus corona mencakup mekanisme proof-
reading.
2. Variabilitas genom mungkin muncul sebagai hasil dari
rekombinasi antara dua lineage virus yang menginfeksi pejamu
yang sama.
3. Mutasi dapat disebabkan oleh sistem pengeditan RNA inang,
yang merupakan bagian dari imunitas alami inang. Sementara
teori genetika populasi menyatakan bahwa mayoritas mutasi
diharapkan netral, beberapa mungkin menguntungkan atau
merusak virus.
Mc Garty TP. Technical Report · January 2021 DOI: 10.13140/RG.2.2.15011.68644
 • Covid-19 virus is so pandemic
in its reach, the fact that so
many people are infected
Why are means we have so many
sources for mutation.
COVID
• It is thus critical to have
mutations so universal immunization, not just
important? so people are not ill, but more
importantly so people do not
become reservoirs for massive
mutation.

3/28/2021 Mc Garty TP. Technical Report · January 2021 DOI: 10.13140/RG.2.2.15011.68644 11

 B.1.1.7 mutant expresses the following
changes
SPIKE
NUCLEOTIDE AMINO ACID
HV 69-70 deletion
21765-21770 deletion HV 69-70 deletion Histidine-Tyrosine deletion
Y144 deletion
21991-21993 deletion Y144 deletion Tyrosine deletion
N501Y, Asparagine to Tyrosine
A23063T N501Y (polar uncharged to hydrophobic)
A570D, Arginine to Aspartic Acid
C23271A A570D (positive to negative side chain)
P681H, Proline to Histidine
C23604A P681H (special to positive charge side chain)
T716I, Threonine to Isoleucine
C23709T T716I (polar uncharged to hydrophobic side chain)
S982A, Serine to Alanine
T24506G S982A (polar uncharged to hydrophobic side chain)
D1118H, Aspartic Acid to Histidine
G24914C D1118H (positive side chain to negative)

Mc Garty TP. Technical Report · January 2021 DOI: 10.13140/RG.2.2.15011.68644

3/28/2021 12
 B.1.1.7 has an unusually large number
of genetic changes, particularly in the
spike protein
1. Mutation N501Y
• One of six key contact residues within the receptor-binding
domain (RBD) and has been identified as increasing binding
affinity to human and murine ACE2.
2. The spike deletion 69-70del
• Evasion to the human immune response but has also occurred a
number of times in association with other RBD changes.
3. Mutation P681H
• Immediately adjacent to the furin cleavage site, a known
location of biological significance.
Mc Garty TP. Technical Report · January 2021 DOI: 10.13140/RG.2.2.15011.68644

3/28/2021 13
 . Evolution of an authentic SARS-CoV-2 escape mutant

Andreano E. bioRxiv preprint doi: https://doi.org/10.1101/2020.12.28.424451

3/28/2021 14
 Top 10 RBD Region Mutations

https://www.cbrc.kaust.edu.sa/covmt/index.php?p=top-rbd-variants-heatmap. Accessed
28/03/2021
 Global

Indonesia

Top 10 RBD Region Mutations Timeline

3/28/2021 16
https://www.cbrc.kaust.edu.sa/covmt/index.php?p=top-rbd-variants-heatmap. Accessed 15 Feb 2021
 COVID-19 virus mutation tracker

https://www.cbrc.kaust.edu.sa/covmt/index.php?p=maps
 High Quality Data Whole Genome Sequences SARS-CoV-2
for Indonesia isolates has been reported to GISAID

Comparison of the number of complete WGS with Mutations of Concerns D614G, N439K, N501Y, and
E484K collection per-month
232 232
WGS Complete

D614G Updated March 25, 2021

N439K 07:18 AM (GMT+7)
N501Y
115113
E484K
8585 81
5049 55
35 39 3735 4040 4444 51 50
29 28
12 1811
2 10 4 41

Maret April Mei Juni Juli Agustus September Oktober November Desember Januari 2021 Februari
2021

Telah ditemukan 700 mutasi D614G sejak April 2020, 143 mutasi
N439K sejak November 2020, 8 mutasi N501Y sejak Januari 2021 dan
1 mutasi E484K pada Februari 2021
https://www.gisaid.org
Data analyzed3/28/2021
from GISAID database 18 18
Prepared by Indri Konsorsium Riset dan Inovasi COVID-19 Kemenristek/BRIN 2021
https://www.gisaid.org/phylodynamics/indonesia/
3/28/2021 20
3/28/2021 21
3/28/2021 22
3/28/2021 23
 Implications for Vaccine Efficacy in Variant B 1.351 or
501Y.V2 (SA)
Pfizer
Scientists have tested the Pfizer
vaccine against N501Y and E484k
mutations in the lab, using blood
samples from vaccinated people.
In that study, vaccination
appeared to work, but was slightly
less effective.
https://doi.org/10.1101/2021.01.27.427998;
Neutralization of SARS-CoV-2 spike 69/70
deletion, E484K, and N501Y variants by 2
BNT162b2 vaccine-elicited sera
Moderna
Moderna vaccine is still effective
against the South Africa variant,
although the immune response
may not be as strong or prolonged.
https://investors.modernatx.com/news-
releases/news-release-details/moderna-covid-19-
vaccine-retains-neutralizing-activity-against
Novavax
In the South Africa Phase 2b clinical
trial, where most of the cases were
the South African variant of the virus,
the vaccine was 60% efficacy (95%
CI: 19.9 – 80.1) for the prevention of
mild, moderate and severe COVID-19
disease was observed in the 94% of
the study population that was HIV-
negative.
https://ir.novavax.com/node/15506/pdf
Johnson & Johnson
The Johnson & Johnson vaccine was
just 57% effective in the South
African part of the trial, where a new
version of the coronavirus is
spreading, compared with 72% in
the US.
https://www.bbc.com/news/health-55857530
AstraZeneca
Oxford-AstraZeneca's vaccine offers
"limited" protection against mild
disease from the South Africa variant,
but experts say it should still protect
against severe disease.
The vaccine appears to be far less
effective against the B.1.351 variant
circulating in South Africa,
according to a yet-to-be-published
analysis released on February 7
South Africa had also greenlighted
the vaccine but announced that it
was halting its rollout after the
results in early February suggested
limited efficacy against the B.1.351
variant.
https://papers.ssrn.com/sol3/papers.cfm?abstract_id=377726
https://www.the-scientist.com/news-
opinion/covid-19-vaccine-frontrunners-67382
24
 • The COVID-19 vaccines that are
currently in development or have
What been approved are expected to
provide at least some protection
impact do against new virus variants because
the new these vaccines elicit a broad immune
response involving a range of
variants of antibodies and cells.
• Therefore, changes or mutations in the
the COVID- virus should not make vaccines
19 virus completely ineffective.
• In the event that any of these vaccines
have on prove to be less effective against one
or more variants, it will be possible to
vaccines? change the composition of the
vaccines to protect against these
variants.

https://www.who.int/news-room/feature-stories/detail/the-effects-of-virus-
3/28/2021
variants-on-covid-19-vaccines 25
 SAFETY IS INVESTIGATED AT EVERY STAGE
OF VACCINE DEVELOPMENT
five ways
that MONITORING AFTER CLINICAL TRIALS

researchers
are GLOBAL CONSENSUS ON ADVERSE EVENTS
RELEVANT TO COVID-19 VACCINES
ensuring
COVID-19 SURVEILLANCE TO DETERMINE
BACKGROUND RATES OF ADVERSE EVENTS
vaccines
are safe. DEVELOPING VACCINE SAFETY PROFILES
 Terima Kasih

3/28/2021 27