Module 2 · Chapter 2
Principles of Immunization and Vaccines
How immunity works, how vaccines are built, what else is in the vial, and when not to vaccinate.
2.1 Immunity
Immunity is the body’s ability to tolerate material indigenous to the body (self) and to identify and eliminate foreign (non-self) material. Most microbes are recognised as foreign, so this protects against infection. Immunity to a microbe is usually indicated by antibodies against it, and is generally specific to one organism or a group of closely related organisms. Two main types: innate and adaptive.
| Innate immunity (2.1.1) | Adaptive immunity (2.1.2) | |
|---|---|---|
| Line of defence | First line | Second line — activated after innate immunity identifies a specific pathogen/antigen |
| Specificity | Not specific; immediate protection against a broad range of invaders | Highly specific; has memory (faster response on re-exposure) |
| Components | Skin, mucous membranes, complement proteins, natural killer cells, phagocytes (neutrophils, macrophages), dendritic cells | Antibodies, T cells and B cells |
| How it acts | Engulfing and digesting invaders, releasing toxic chemicals, activating the adaptive response | Two arms: humoral and cell-mediated |
Humoral (antibody-mediated)
With help from helper T cells, B cells differentiate into plasma B cells that produce antibodies against a specific antigen. Deals with antigens freely circulating / outside infected cells. Antibodies bind antigens → neutralisation, lysis (dissolution of cells by a lysin) or phagocytosis.
Cell-mediated
Occurs inside infected cells, mediated by T lymphocytes. Antigens are expressed on the cell surface or an antigen-presenting cell. Helper T cells release cytokines that help activated T cells bind the infected cell’s MHC–antigen complex and become cytotoxic T cells; the infected cell undergoes lysis.
Active vs passive immunity
| Active | Passive |
|---|---|
| Host’s own immune system produces an antigen-specific response. Usually lasts many years, often lifelong. Acquired by (a) surviving infection/antigen exposure → memory cells that rapidly re-make antibodies on re-exposure; or (b) vaccination — a response similar to natural infection without the disease and its complications. | Transfer of antibodies made by one human or animal to another. Protective but temporary — antibodies degrade. Commonest form: mother → infant (protects for a few months to a year). Giving specific antibodies (e.g. anti-diphtheria toxin) gives immediate but transient immunity. |
Effective immunization must induce long-term stimulation of both humoral and cell-mediated arms, producing effector cells for the current exposure and memory cells for future infection.
Factors influencing the response to vaccination: maternal antibody or antibody from prior natural infection; nature and dose of antigen; route of administration; presence of an adjuvant (e.g. aluminium-containing material). Host factors: age, nutrition, genetics, coexisting disease.
2.1.3 Herd (community) immunity
- Vaccinating a portion of the population also protects unprotected individuals; the chain of infection breaks when large numbers become immune (for diseases spread person to person).
- More immune people → lower chance a susceptible person meets an infectious one.
- Diseases usually disappear before coverage reaches 100% — seen with smallpox, poliomyelitis and measles.
- Herd immunity threshold = proportion immune above which a disease may no longer persist. It varies with virulence of the disease, vaccine efficacy, population composition and distribution of vaccinated/unvaccinated people.
2.1.4 How immunization works
- All vaccines prepare the immune system to attack infection; the key result is long-lived memory lymphocytes that respond faster and more coordinated to later infection. Protection is not always complete, but severity is usually reduced.
- Primary response (priming): first exposure; takes time. IgM appears first — small amounts, binds weakly. After a few days, IgG — more specific and longer-lasting (Figure 2.1).
- Secondary response (later dose of same vaccine): much faster, predominantly IgG; may eliminate pathogens before any damage occurs.
2.2 Vaccines
A vaccine is a biological product that improves immunity to a disease. It contains a disease-causing microorganism or part of it — live-attenuated or inactivated microbe, a sub-component protein (toxin or surface protein), RNA or DNA.
- Monovalent: single strain of a single antigen (e.g. measles vaccine).
- Polyvalent: two or more strains/serotypes of the same antigen (e.g. OPV, HPV, influenza).
- Combined: two or more different antigens (e.g. DTwP, DTP-HepB-Hib/pentavalent). Advantages: lower stocking cost and cold-chain space, better compliance (fewer pricks), fewer visits, better timeliness, easier addition of new vaccines.
- No evidence that several antigens overload the immune system (it can respond to millions at a time). Combining usually does not increase adverse reactions and may reduce them overall.
2.2.1 Four broad types used in routine immunization
| Type | Key features | Examples (text + Figure 2.2) |
|---|---|---|
| A. Live-attenuated (LAV) | Wild virus/bacteria weakened by repeated culture. Replicates in the vaccinee and produces immunity virtually identical to natural infection, usually without illness. Can cause disease in the immunocompromised → contraindicated; generally contraindicated in pregnancy (theoretical foetal risk). First dose usually protects; extra dose ensures seroconversion — measles: 95–98% respond to one dose, second dose is “insurance” (~100%). Long-lasting; no boosters needed except OPV (multiple doses). Affected by circulating antibodies (maternal/prior infection). Labile — damaged by heat and light. | Viruses: measles, mumps, rubella, varicella, yellow fever, OPV, rotavirus, influenza (intranasal), JE (live), shingles, dengue. Bacteria: BCG, oral typhoid. |
| B. Inactivated (killed) whole-cell | Grown in culture then inactivated by heat or chemicals (usually formalin). Cannot grow or cause disease, even in immunodeficient persons; generally safer than LAV; usually not affected by circulating antibodies; more stable. Always need multiple doses — first dose only primes. Response mostly humoral, little cellular. Titres wane → periodic boosters. | IPV, hepatitis A, rabies; whole-cell pertussis, JE (inactivated), cholera. |
| C. Subunit (purified antigen) | Only the antigens that best stimulate immunity → no risk of illness, fewer reactions. Made by purifying components from culture (e.g. acellular pertussis, meningococcal B) or by recombinant DNA (recombinant subunit vaccines). | See C.1–C.3 below. |
| D. Toxoid | Disease caused by secreted toxin (diphtheria, tetanus). Toxin purified and chemically altered (usually formaldehyde) — non-toxic but still induces protective immunity. | Tetanus toxoid, diphtheria toxoid. |
C.1 Protein-based recombinant
Hepatitis B: HBV gene segment inserted into yeast → large amounts of HBsAg, purified. Identical to natural HBsAg, contains no viral DNA, cannot infect. Acellular pertussis (aP) contains inactivated pertussis toxin (protein).
C.2 Polysaccharide
Only the sugar capsule of the bacterium is the antigen. Meningococcal and pneumococcal polysaccharide vaccines — purified, non-infectious capsules.
C.3 Conjugate
Children under 2 years respond poorly to polysaccharides (T-cell independent). Chemically linking (conjugating) the polysaccharide to a protein enables T-cell recognition → strong response and memory. Examples: Hib, PCV (7/10/13-valent), meningococcal A and B.
Annexure 1 lists the strain and type of every UIP and non-UIP vaccine — see the Annexures module.
COVID-19 vaccines (Table 2.1)
Intended to give acquired immunity against SARS-CoV-2. Developed globally on viral-vectored, protein subunit, nucleic acid (DNA, RNA), live-attenuated and inactivated platforms.
| Platform | Brands (manufacturer) | How it works |
|---|---|---|
| mRNA | Comirnaty (Pfizer/BioNTech), Spikevax (Moderna), Gemcovac-19 (Gennova) | Instructions for cells to make part of the spike protein, which triggers a protective response. |
| Viral vector | Vaxzevria (AstraZeneca), Covishield (Serum Institute of India), Jcovden (Janssen), Sputnik V, Sputnik Light, iNCOVACC (Bharat Biotech, intranasal) | A modified different virus delivers spike instructions. Sputnik V was the first to use heterologous boosting — two different vectors in two shots. |
| Inactivated virus | Coronavac (Sinovac), Sinopharm, Covaxin (Bharat Biotech) | Killed virus/particles recognised by the immune system. |
| Recombinant spike protein / nanoparticle (subunit) | Novavax and Covovax (Serum Institute), Corbevax (Biological E) | Selected spike fragments produce a strong response. |
| Plasmid DNA | ZyCoV-D (Zydus Cadila) | Spike-coding DNA inserted into a bacterial plasmid; cells make spike protein; antibodies follow. |
2.2.2 Other components (excipients)
| Excipient | Purpose | Examples / notes |
|---|---|---|
| Adjuvants | Enhance degree and/or duration of response → less antigen or fewer doses | Aluminium salts (hydroxide, phosphate, potassium aluminium sulphate) — mainly enhance response to proteins. Newer: liposomes, squalene emulsified with surfactants (AS03). Safe over decades; rarely injection-site reactions — subcutaneous nodules, sterile abscess, granulomatous inflammation, contact hypersensitivity. |
| Antibiotics | Prevent bacterial contamination of tissue culture during manufacture | MMR and IPV contain <25 micrograms neomycin per dose (<0.000025 g). Known neomycin allergy → observe closely after vaccination. |
| Preservatives | In killed/subunit vaccines: inactivate viruses, detoxify toxins, prevent secondary bacterial/fungal contamination | Thiomersal, formaldehyde |
| Stabilisers | Control pH, stabilise antigens through freeze-drying, stop antigen sticking to glass (loss of immunogenicity) | Potassium or sodium salts, lactose, human serum albumin, gelatin, bovine serum albumin |
| Trace elements | Residues from manufacture | Formaldehyde, residual cell-culture materials |
Trace amounts matter only for people allergic to them.
2.3 Contraindications and precautions
- A contraindication is a rare condition in a recipient that increases the risk of a serious adverse reaction or disease due to host factors. Ignoring it can cause avoidable reactions.
- Most contraindications are temporary — vaccinate later. Children with moderate or severe acute illness should not be vaccinated until they improve.
- The serious (life-threatening) reaction of concern is anaphylaxis; the other risk is infection from a live vaccine in immunocompromised people.
General contraindications (MoHFW Immunization Handbook 2018)
- Documentation or history of anaphylaxis or other severe reaction to a previous dose of the vaccine or a vaccine component.
- Live vaccines must not be given to immunodeficient children and pregnant women — e.g. do not give measles-containing vaccine to HIV-infected children while still immunodeficient. LAVs are generally contraindicated in pregnancy (theoretical foetal risk).
For vaccine-specific contraindications, refer to the manufacturer’s product insert.
Precautions are not contraindications — they are conditions to weigh when deciding if benefits outweigh risks (especially in immunocompromised or pregnant people). Treating precautions in product inserts as absolute contraindications leads to missed opportunities to vaccinate.
Chapter summary
- Immunity = defence against bacteria, viruses, fungi and parasites; innate (present from birth, no prior exposure) or adaptive (develops after exposure).
- B and T cells produce antibodies, destroy infected cells and coordinate the response.
- Active immunity follows infection or vaccination; passive immunity comes from external antibodies (placenta, breast milk, immunoglobulins).
- Vaccines are given before exposure and are made from weakened/inactivated pathogens, proteins/subunits or genetic material (e.g. mRNA).
- Vaccines contain immunogens plus excipients (adjuvants, antibiotics, preservatives, stabilisers, trace elements) — the body may react to any of these.
- Herd immunity: when enough people are immune, spread becomes unlikely.
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