Vaccine Development: Principles, Mechanism and India’s COVID-19 Approach

A vaccine teaches the immune system to recognise a pathogen before it strikes.

Vaccines have eradicated smallpox and pushed polio to the edge of extinction.

A 5 ml vial of Covaxin used in a sub-district in Bihar during India’s COVID-19 vaccination drive. Photo: DTM, CC BY-SA 4.0, via Wikimedia Commons.

Vaccines & India’s COVID-19 Push

SciTech0205

Principles of vaccine development and India’s 2021 responses.

2021

First indigenous vaccine

Covaxin, EUA January

Covishield

Viral-vector vaccine

ChAdOx1 adenovirus

ZyCoV-D

DNA vaccine

first of its kind

220+ cr

Doses by early 2023

national drive

India administered 220+ crore doses by early 2023.

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Must Know

The Basic Principle and How Vaccines Work

The basic principle of vaccination

PrincipleA vaccine mimics an infection so the body learns to fight the real pathogen.
MemoryThe immune system remembers a first encounter and reacts faster next time.
SafetyVaccines train immunity without the risk of serious disease.
OutcomeLater exposure triggers a quick, strong response that blocks illness.

How vaccines work step by step

AntigenThe vaccine introduces a harmless antigen, a piece of the pathogen.
B CellsB cells make antibodies that bind and neutralise the antigen.
T CellsT cells destroy infected cells and coordinate the immune response.
MemoryMemory B and T cells persist for years after the response fades.
ProtectionOn real infection, memory cells multiply fast and stop the disease.

Key players: antigen, antibody, B cells, T cells

AntigenAn antigen is any molecule the immune system recognises as foreign.
AntibodyAntibodies are Y-shaped proteins that latch onto antigens.
B CellsB cells produce antibodies and become memory cells.
T CellsHelper T cells switch on other cells; killer T cells destroy infected cells.
MemoryMemory cells are the lasting record of every vaccine encounter.

The main vaccine platforms

Live AttenuatedLive attenuated vaccines use a weakened version of the live pathogen.
InactivatedInactivated vaccines use killed whole pathogens or their fragments.
SubunitSubunit vaccines use a purified protein or sugar piece of the pathogen.
Viral VectorViral vector vaccines use a harmless virus to carry a pathogen gene.
Nucleic AcidmRNA and DNA vaccines carry genetic instructions for one protein.
ToxoidToxoid vaccines neutralise bacterial toxins that cause disease.

Good to Know

India’s COVID-19 Vaccine Approaches

Covaxin: the inactivated whole-virion approach

PlatformBharat Biotech built Covaxin from whole SARS-CoV-2 particles killed in the lab.
ProductionThe virus was grown in Vero cells and then inactivated with chemicals.
AdjuvantAn added adjuvant, Alhydroxiquim-II, boosts the immune response.
ApprovalCovaxin received emergency use approval in India in January 2021.
FirstIt became the first indigenous COVID-19 vaccine developed in India.

Covishield: the viral vector approach

LicenceSerum Institute of India made Covishield under licence from Oxford-AstraZeneca.
VectorA weakened chimpanzee adenovirus, ChAdOx1, carries the spike protein gene.
MechanismThe harmless vector delivers the gene, and cells display the spike protein.
ResponseThe immune system then builds antibodies against the spike.
ApprovalCovishield received emergency use approval in India in January 2021.

Sputnik V and the heterologous prime-boost

VectorsSputnik V uses two different adenovirus vectors, Ad26 and Ad5.
DesignThe first dose uses Ad26; the second uses Ad5 as a booster.
LogicUsing two vectors avoids immunity against the first vector.
IndiaDr. Reddy’s Laboratories imported and distributed Sputnik V in India.

ZyCoV-D: India’s DNA plasmid vaccine

PlatformZydus Cadila developed ZyCoV-D, a plasmid DNA vaccine.
GeneThe plasmid carries the gene for the SARS-CoV-2 spike protein.
DeliveryA needle-free injector, PharmaJet Tropis, delivers the vaccine.
DosesZyCoV-D needs three doses for full protection.
ApprovalIndia granted emergency use approval to ZyCoV-D in August 2021.

Corbevax: the protein subunit approach

PlatformBiological E made Corbevax from the spike protein’s receptor-binding domain.
SourceThe technology came from Baylor College of Medicine and Texas Children’s Hospital.
AdjuvantAlum-based adjuvants strengthen the immune response.
RoleCorbevax served as a booster in India’s national programme.

mRNA and intranasal vaccines

HGCO19Gennova’s HGCO19 was India’s first mRNA vaccine, approved in 2022.
iNCOVACCBharat Biotech’s iNCOVACC is an intranasal adenoviral vaccine.
NasalIt is sprayed into the nose and builds immunity at the entry point.
BoosteriNCOVACC was approved as a booster dose in September 2022.

The national COVID-19 vaccination drive

StartIndia’s COVID-19 vaccination drive began on 16 January 2021.
PlatformThe Co-WIN platform managed registrations and doses digitally.
PriorityHealthcare workers, frontline workers and the elderly went first.
ScaleIndia administered more than 220 crore doses by early 2023.

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Herd Immunity, Safety and Delivery

Herd immunity and why it matters

ConceptWhen enough people are immune, the virus struggles to spread.
ProtectionHerd immunity shields those who cannot take vaccines.
ThresholdThe threshold depends on how contagious the disease is.
VariantsNew variants can lower vaccine protection and raise the threshold.

Efficacy versus effectiveness

EfficacyEfficacy is vaccine performance measured in controlled trials.
EffectivenessEffectiveness is performance in real-world populations.
RealityEffectiveness is usually lower than trial efficacy.

Vaccine safety and adverse events

AEFIAdverse events following immunisation are tracked by regulators.
CommonMild fever and soreness are common and short-lived.
RareSerious side effects are rare and carefully investigated.
SurveillanceIndia’s AEFI surveillance system records and reviews every report.

Cold chain and vaccine logistics

Cold ChainMost vaccines need continuous refrigeration from factory to arm.
StorageDifferent vaccines need different temperature ranges.
NetworkIndia’s cold chain reaches the last village through health workers.
Last MileVaccine carriers and ice boxes protect doses on every route.

India’s immunisation architecture

UIPThe Universal Immunisation Programme covers major vaccine-preventable diseases.
MissionMission Indradhanush targets children missed by routine immunisation.
EquityVaccination must reach every child, rich or poor, urban or rural.

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