Sputnik V – The First Registered COVID-19

Vaccine
August, 2020
Agenda

•1 The Gamaleya Research Center

•2 Vaccine overview
•3 Clinical trials status
•4 Production process requirements
 MINISTRY OF HEALTH OF RUSSIAN FEDERATION
National Research Center of Epidemiology and Microbiology n. a. N.F. Gamaleya

SARS-COV-2 Vaccine
working group
Alexander Gintsburg
The Head of the National Research Center of Epidemiology and
Microbiology n. a. N.F. Gamaleya

SCIENTIFIC DEPARTMENT CLINICAL TRIALS GROUP PILOT SCALE

MANUFACTURING
Denis Logunov Nadezhda Lubenec
Scientific director of the Center, Alexander Semikhin
Lab. Cellular Microbiology Elizaveta Tokarskaya
Inna Dolzhikova
Lab. Russian State Collection of Viruses Yana Simakova

Daria Egorova
Lab. Genetic engineering of pathogenic LEGAL DEPARTMENT RUSSIAN DIRECT
microorganisms INVESTMENT FUND
Maxim Shmarov
Elena Domogarova
Lab. Molecular biotechnology
Agenda

•1 The Gamaleya Research Center

•2 Vaccine overview
•3 Clinical trials status
•4 Production process requirements
 ADENOVIRUS BASED VECTOR VACCINE OVERVIEW

• Sputnik V – vaccine developed by the Gamaleya National Research Center of Epidemiology

and Microbiology, which has over 20-years history of vector vaccines development and
successfully created effective vaccines against Ebola virus and MERS virus (the Middle East
respiratory syndrome).

• Adenovirus vector vaccine contains a sequence coding S protein - a protective antigen for
SARS-COV-2 viral infection.

• A vector vaccine based on the adenovirus partially imitates a viral infection process — by
penetrating inside the body's cells, it causes an extended expression of the antigen, forming
both of a high titer of antibodies and a cell-mediated response.

• A technology for manufacturing of vector vaccines based on adenoviruses is well-developed.

• Vaccine is done in 2 shots – the second one is done on the 21st day from the first shot. Two
components represent 2 different vector serotypes – Ad26 and Ad5. Combination of different
vector types allows to form long lasting immunity.

• Johnson & Johnson followed this approach with the focus on Ad26 which is only one of two
vectors used by the Gamaleya National Research Center of Epidemiology and Microbiology
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 landscape of COVID-19 candidate vaccines – 21 July 2020

University of
Oxford/AstraZeneca;
CanSino Biological
Inc./Beijing Institute of
Biotechnology;
Gamaleya Research
Institute

Sinovac
Wuhan Institute/Sinopharm
Beijing Institute/Sinopharm

Anhui Zhifei Longcom

Biopharmaceutical;
Novavax

Moderna; Inovio; AnGes/ Takara Bio

Genexine; Cadila Healthcare
 Vaccine types against viral pathogens
Vaccine type Advantages Disadvantages Examples COVID-19 vaccine
Developers (examples)
Live • Imitation of the whole infection • Low Stability Priorix Tetra, ProQuad
attenuated process Rotarix, Rotavac
• Risk of lack of attenuation Zostavax
• Both antibody and cellular immunity Flumist
• Risk of restoring pathogenicity Stamaril
• Long lasting immunity
• Potential for over-attenuation with
associated poor immunogenicity
Inactivated • Stable • Reduced immunogenicity Tritanrix, Havrix, Vaqta
Rabipur
• Low cost manufacturing • Reactogenicity Encepur
Ixiaro
• Short immunity Dukoral

Split and • Low reactogenicity • Reduced immunogenicity Fluarix, Fluarix Tetra, Flulaval,
subunits Intanza, Vaxigrip Engerix B,
• Easily developed • Mostly antibodies rather than cellular Recombivax Cervarix, Gardasil,
immunity Gardasil Bexsero, Trumenba
Mosquirix
• Short immunity Shingrix

• Need adjuvant
Vector • Use pathways that induce robust and • Efficacy decreased by pre-existing Boostrix, Gamaleya
durable both cellular and humoral vector immunity Infanrix
immunity Adacel Research
• Vector-specific responses may limit GamEvac combi Center
• Easily engineered subsequent doses

• Both antibody and cellular immunity

• Act as adjuvant due to a vector

properties
DNA/RNA • Easily engineered • Instability of the mRNA and Only for veterinary use (DNA
manufacturing problems vaccines)

• Need delivery system

• No one registered for human use

 GAM-COVID-VAC and GAM-COVID-VAC-lyo

Component 1
SARS-CoV-2
Glycoprotein S
rAd26-S

Component 2

rAd5-S

VACCINATION REGIMEN:
Component 1 Component 2 Vaccine Key compound Form Storage

Gam-COVID-Vac Comp. 1: rAd26-S Liquid -20oC

Comp. 2: rAd5-S

1 21 DAYS Gam-COVID-Vac Lyo Comp. 1: rAd26-S Lyophilized +4oC

Comp. 2: rAd5-S
 Other Ad vector types in development
The same S protein gene for all Different adenovirus vector types in development:
current vector vaccines but
different Ad-based vector types University of Oxford/AstraZeneca
ChAdOx1 for both prime and boost immunization Loss of boost
immunization
CanSino Biological Inc./Beijing Institute of Biotechnology efficacy due anti-
Ad5 for both prime and boost immunization vector response

Johnson & Johnson

Ad26 for both prime and boost immunization

High efficacy of
Gamaleya Research Center
both prime and
Ad26 for prime administration
boost
Ad5 for boost immunization
immunization

Ad vector type Host Registered vaccines

Ad5 Human SARS-COV-2 (CanSino)
Ebola (Gamaleya NRCEM)
Ad26 Human Ebola (J&J)

ChAd Chimpanzee None

Advantages of two different vectors during immunization

HOMOLOGOUS
IMMUNIZATION

HETEROLOGOUS
IMMUNIZATION
Agenda

•1 The Gamaleya Research Center

•2 Vaccine overview
•3 Clinical trials status
•4 Production process requirements
PRECLINICAL RESEARCH PROGRAM OF THE
VACCINE EFFICACY

• IMMUNOSUPPRESSED SYRIAN HAMSTERS LETHAL

MODEL of SARS-COV-2 INFECTION

• IMMUNOGENICITY STUDIES:
BALB/C, C57BL/6 mice
Syrian hamsters
Marmosets (Callithrix jacchus)
Rhesus macaque (Macaca mulatta)
 GAM-COVID-VAC and GAM-COVID-VAC-lyo

• Vaccine elicit robust humoral and cellular immune

response.

• Lethal model on immunosuppressed Syrian hamsters:

Vaccine protects 100% animals from lethal infection
with SARS-CoV-2.
 Clinical trials and Regulatory

• Clinical trials phase I/II (in Russia) finished. There is no scientific or

clinical evidence of any side effects associated with the vaccine.
– Gam-COVID-Vac Vaccine Against COVID-19 ClinicalTrials.gov
Identifier: NCT04436471
– Gam-COVID-Vac Lyo Vaccine Against COVID-19 ClinicalTrials.gov
Identifier: NCT04437875
• Vaccine was registered on 11th of Aug 2020
• Pivotal trial phase III
• Volunteers recruitment of 2000 people for phase III in Russia and
over 1000 people in the Middle East

For more information: https://sputnikvaccine.com/

Agenda

•1 The Gamaleya Research Center

•2 Vaccine overview
•3 Clinical trials status
•4 Production process requirements
 Manufacturing and Technology Transfer

• Manufacturing capacity at launch - 2 million doses a month,

projected manufacturing capacity 6 million a month by Dec
2020.

• Technology transfer options including dosage form and API

manufacturing

• Accepts commitments to pre-order and secure manufacturing

capacity and technology transfer
ADENOVIRUS BASED VECTOR VACCINE PRODUCTION PROCESS

Step 1: Cultivation Step 2: Purification

Inoculating of special
HEK cells in optimized
nutrient medium
Vector amplification Separation of infected Purification of virus using
and expansion in cells from medium by Chromatography
Wave Bioreactors Centrifugation
Inoculation of Ad5 or
Ad26 vector
Storage for infected
cell mass -40o C)

Step 3: Vaccine production

Lyophilization in Sterilization through Mixture of separated

isolator (for dry form filtration virus with buffer
only)

Filling in ampoules / Step 4: End product

Dry form syringes / vials (liquid
of vaccine form)

Storage for dry form: Storage for liquid

+2 - +8o form: freezing +4o C for finished product
(-18 - -20o C)
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 CRITICAL EQUIPMENT LIST

Step 1: Cultivation

1 WAVE bioreactor – Sartorius

2 CO2 incubator shaker – Sartorius

3 Centrifuge – Beckman

4 Rotor to centrifuge – Beckman

Step 2: Separation

5 Chromatography system – GE

Step 3: Vaccine production

6 Refrigerator container

7 Lyophilizer (only for dry form production)

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EXAMPLE: REQUIRED EQUIPMENT TO PRODUCE 60K DOSES OF
2-COMPONENT VACCINE PER MONTH

Step 1: Cultivation Quantity

1 Wave bioreactor (fermenter) 4x 50-liter bioreactors

2 CO2 incubator shaker 4x

3 Centrifuge 4х for 4x 50-liter bioreactors

4 Rotor to centrifuge

Step 2: Separation

5 Chromatography system 1x enough if columns are changed sequentially

Step 3: Vaccine production

6 Refrigerator container 1x enough

7 Lyophilizer (only for dry form production) 1x enough

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