PERAN SAINS DALAM PANDEMI

Amin Soebandrio

Many unknowns including

• Disease and its optimal management

• Virus reservoirs (the origin?)

• Virus evolution

• Transmission and epidemiology

Urgent need to develop safe and effective countermeasures that can be available, accessible and suitable for use in populations most in need

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State-of-the-art

In-house RT-PCR detection in place

Ready-to-use formulations on research use only basis available,

in vitro diagnostic-qualified products in the pipeline

Virus isolation capacities available in reference centers

Generic sequencing capacities widely available

Virus isolates available under minimal material transfer agreements

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Required Capacities

PreventPredict

Detect

Resp

onse

Report

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VACCINE TECHNOLOGIES

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Old Technology

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• Grow in animals (vaccinia in calves for smallpox; rabbit brains for rabies)

• Simple bacterial culture (Cholera vibrio) then inactivation

• Grow in eggs (influenza, vaccinia) then inactivate

Live attenuated virus vaccines

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• Previous preparation:

• Passage at low temperature

• Chemical mutagenesis and selection of mutants with desired phenotype*

• Passage in heterologous tissues

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MODERN MOLECULAR BIOLOGYHAS OFFERED NEW APPROACHES TO MAKE VACCINES

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Virosome

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Clone gene from virus or bacteria and express this protein antigen in yeast, bacteria or mammalian cells in culture

Cloned gene

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Cloned protein antigenshave pluses and minuses

Pluses

• Easily manufactured and often

relatively stable

• Cannot “revert” to recreate pathogen

Minuses

• Poorly immunogenic

• Poor T cell response

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Virus Vector

Clone gene from virus or bacteria Into genome of another virus (adenovirus, canary pox, vaccinia) and use this live virus as vaccine

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Viral vectors have pluses and minuses

Pluses

• Infects human cells but some do not replicate

• Better presentation of antigen

• Generate T cell response

Minuses

• Can cause bad reactions

• Can be problems with pre-exisiting immunity to virus

• Often can only accommodate one or two antigens

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Reassortment (1)

Courtessy of National Institute of Allergy

and Infectious Diseases (NIAID)

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Reassortment (2)

Courtessy of National Institute of Allergy

and Infectious Diseases (NIAID)

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Reverse Genetics (1)

Frontiers in Bioscience 4912-4924, May 1, 20085 /23 /2020 16

Reverse Genetic (2)

Courtessy of National Institute of Allergy

and Infectious Diseases (NIAID)

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Recombinant protein vaccines• Advantages :

• no risk of infection (residual live virus) ‏• no side-effect (JEV) ‏• Codon optimized

• Disadvantage : • Identification of the right immunogen• High production of rec. protein (promoter and gene amplification

• Separation of the protein from host cell proteins and DNA (secreted protein) ‏• Gentle procedure to purify proteins without denaturation: Purification using immunoaffinity (MAb) or IMAC (His tag)

or lectin chromatography, physical separation: maintain the 3D structure and function for Nt Ab induction• Several injections• Choice of adjuvant

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Recombinant antigens

Expression systems

• Bacteria

• Yeast

• Mammalian cells

• Insect cells

• Avian cells

• Plants

• DNA ( Gene gun. B and T cell response) ‏

Type of antigens

• Particulate (VLP) ‏• Soluble (monomeric or dimeric) ‏• Fusion protein

• Chimeric

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5/23 /2020

Overview of Potential SARS-CoV-2 Vaccine Platforms

Amanat and Krammer, SARS-CoV-2 Vaccines: Status Report, Immunity (2020), https://doi.org/10.1016/j.immuni.2020.03.007

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Overview of Vaccine Production Platforms and Technologies for SARS-CoV-2

Amanat and Krammer, SARS-CoV-2 Vaccines: Status Report, Immunity (2020), https://doi.org/10.1016/j.immuni.2020.03.007

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Pipeline of COVID-19 vaccine candidates by technology platform.

https://www.nature.com/articles/d41573-020-00073-55/23 /2020 22

Profile of COVID-19 vaccine developers by type and geographic location.

https://www.nature.com/articles/d41573-020-00073-5

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CLINICAL-PHASE VACCINE CANDIDATES FOR COVID-19 Candidate Vaccine characteristics Lead developer Status

mRNA-1273LNP-encapsulated mRNA vaccine

encoding S proteinModerna Phase I (NCT04283461)

Ad5-nCoVAdenovirus type 5 vector that

expresses S proteinCanSino Biologicals Phase I (NCT04313127)

INO-4800DNA plasmid encoding S protein

delivered by electroporationInovio Pharmaceuticals Phase I (NCT04336410)

LV-SMENP-DC

DCs modified with lentiviral

vector expressing synthetic

minigene based on domains of

selected viral proteins;

administered with antigen-specific

CTLs

Shenzhen Geno-Immune Medical

InstitutePhase I (NCT04276896)

Pathogen-specific aAPC

aAPCs modified with lentiviral

vector expressing synthetic

minigene based on domains of

selected viral proteins

Shenzhen Geno-Immune Medical

InstitutePhase I (NCT04299724)

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Difference between Traditional Vaccine Development and Development Using a Pandemic Paradigm.

https://www.nejm.org/doi/full/10.1056/NEJMp20056305/23 /2020 25

HERD IMMUNITY

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