Vaccines and Immunoprophylaxis

Two Routes

Active (vaccination) — stimulates own immune system, lasting memory. Passive (immunoglobulin) — ready-made Ab, immediate but temporary, bypasses own immune system.

Vaccination

Vaccine = immunobiological preparation, specific protection. Immunogen → active immunity (Ab and/or T cell response).

History: “Variolae vaccinae” = cowpox (Jenner). Pasteur generalized term “vaccine” (honoring Jenner).

Valency: Monovalent (1 antigen/serotype) vs Polyvalent (multiple strains, e.g. trivalent flu/polio).

Homologous (same organism) vs Heterologous/Jennerian (different organism):

• Jenner: cowpox → smallpox protection
• BCG (M. bovis) → M. tuberculosis protection

Live Attenuated Vaccine

Live organism, attenuated via serial passage (chick embryo/tissue culture/animal). Smallpox vaccine = EXCEPTION, not attenuated (uses naturally nonpathogenic vaccinia/cowpox).

Advantages over killed: organism multiplies (larger effective dose), retains ALL immunogenic components, induces mucosal immunity (secretory IgA).

Precautions:

• Contraindicated: immunodeficiency, malignancy, immunosuppressive/steroid Rx
• Contraindicated in pregnancy (unless infection risk > fetal harm risk)
• 2 live vaccines: ≥4 week gap. EXCEPTION: yellow fever after MMR can be <4wk
• Single dose usually. EXCEPTION: OPV (multiple spaced doses)
• Risk of reversion to virulence if attenuation imperfect
• Storage critical (esp. OPV, measles)

Examples: Bacterial — BCG, Typhoral, Epidemic typhus vaccine Viral — Measles, Mumps, Rubella, Live flu, Chickenpox, OPV (Sabin), Rotavirus, Yellow fever 17D, Hepatitis A, JE (14-14-2 strain)

Inactivated/Killed Vaccine

Grown in culture → killed (heat/formaldehyde). Safer, LESS efficacious. Needs: large dose, adjuvant (alum in DPT), multiple doses + booster. Route: SC/IM. Only absolute contraindication: severe reaction to previous dose.

Examples: Bacterial — Typhoid, Cholera, Pertussis, Plague Viral — IPV (Salk), Killed flu, Rabies, Hepatitis A, JE

Killed vs Live Comparison

Other Vaccine Types

Toxoid: detoxified exotoxin (acid pH/formalin/storage) — loses virulence, keeps immunogenicity. Neutralizing Ab vs TOXIN not organism. DT, TT.

Extracted/cellular fraction: purified component. Meningococcal, Pneumococcal, Hib vaccine (capsular polysaccharide).

Subunit: single component. Hepatitis B (HBsAg), HPV vaccine. Made by recombinant DNA tech (gene inserted into yeast → mass produces antigen).

Combination: multiple agents, simplifies administration ± boosts immunogenicity. DPT — pertussis acts as adjuvant for diphtheria+tetanus toxoid.

Newer Approaches

DNA vaccine (experimental): DNA fragment with pathogen gene injected → integrates → host transcribes protein → immune response.

Edible vaccine (experimental): gene for oral antigen → transgenic plant (banana/potato) → mass antigen production → oral consumption. Advantages: low cost, scalable, oral, local immunity, heat stable. Examples: transgenic potato/tomato (diarrheagenic organisms), edible banana (Norwalk virus).

Cold Chain

System: manufacturer → storage → administration site, unbroken temperature control. Refrigerated: +2°C to +8°C. Frozen: ≤-15°C. Some need light protection too.

Broken cold chain = commonest vaccine failure cause. OPV = MOST heat-sensitive, needs -20°C. Freezer compartment: Polio, Measles vaccine. Cold (NEVER frozen): DPT, TT, Td, BCG, Hepatitis B, Hib, diluents.

Vaccine Vial Monitor (VVM): heat-sensitive label. Outer blue circle (not heat sensitive) + inner white square (darkens with heat exposure). Stage 1 (white) / Stage 2 (light blue) = USABLE. Stage 3 (blue, = circle) / Stage 4 (dark blue) = DISCARD.

National Immunization Schedule (NIS) 2020, India

Pregnant women: TT/Td-1 (early pregnancy) → TT/Td-2 (4wk later, <36wk) → TT/Td booster (if 2 doses within last 3yr).

Infants:

• BCG at birth (0.05mL ID, left upper arm)
• Hep B birth dose within 24hr
• OPV-0 within 15 days
• OPV 1,2,3 + Pentavalent (DPT+Hib+HepB) 1,2,3 at 6,10,14 weeks
• PCV at 6+14wk, booster 9-12mo
• Rotavirus at 6,10,14wk
• IPV: 2 FRACTIONAL doses (ID) at 6+14wk
• Measles/MR 1st dose + JE-1 at 9-12 completed months
• Vitamin A 1st dose (with MR)

Children:

• DPT booster-1, MR 2nd dose, OPV booster, JE-2 at 16-24 months
• Vitamin A 2nd-9th dose, every 6 months to age 5
• DPT booster-2 at 5-6 years
• TT/Td at 10 and 16 years

Rotavirus + PCV = selected states only (not nationwide yet).

Passive Immunoprophylaxis

Immediate effect, bypasses recipient’s immune system. Used for:

• Immunocompromised (can’t make own Ab)
• Post-exposure prophylaxis (need immediate protection)
• Toxin-mediated disease treatment (antibiotics can’t neutralize toxin)

Two Routes to Protection

Immunoprophylaxis against microbial disease works through two fundamentally different mechanisms: active immunoprophylaxis (vaccination), which stimulates the recipient’s own immune system to build lasting protective memory, and passive immunoprophylaxis (immunoglobulin administration), which supplies ready-made antibody directly, bypassing the recipient’s own immune apparatus entirely for an immediate but temporary effect.

Vaccination

A vaccine is an immunobiological preparation providing specific disease protection — the immunogen it contains stimulates the immune system to build active immunity, as protective antibody and/or a competent T cell response. The term derives from Variolae vaccinae (cowpox), Edward Jenner’s term for the cowpox material he used to protect against smallpox; Louis Pasteur later generalized “vaccine” to cover every such protective preparation, in Jenner’s honour.

Vaccines can be monovalent (single antigen/serotype) or polyvalent (several strains of the same organism, e.g. trivalent influenza or polio vaccine). Most are homologous — made from the same organism the disease is caused by — but a few are heterologous (Jennerian), using a related but different organism: Jenner’s original cowpox-for-smallpox strategy, and BCG (from Mycobacterium bovis) protecting against M. tuberculosis.

Live Attenuated Vaccines

Prepared from live organisms that have lost disease-causing capacity through serial passage in a foreign host (chick embryo, tissue culture, or live animals) while retaining immunogenicity. (Smallpox vaccine is the one live vaccine that is not attenuated — it simply uses the naturally nonpathogenic, cross-reactive vaccinia/cowpox virus directly.)

Live vaccines are generally more potent than killed ones because the organism actually multiplies in the host (delivering a larger effective antigenic dose than what was injected), retains every major and minor immunogenic component, and induces genuine mucosal immunity via secretory IgA.

Precautions: contraindicated in immunodeficiency, malignancy, or on immunosuppressive/corticosteroid therapy; contraindicated in pregnancy unless infection risk outweighs fetal harm risk; two live vaccines need at least a 4-week gap (except yellow fever after MMR, which can be given sooner); most are single-dose (the notable exception being oral polio vaccine, which needs multiple spaced doses); attenuation must be done properly, since there is always a theoretical risk of reversion to virulence; and storage (especially of OPV and measles vaccine) is temperature-critical.

Examples: BCG, typhoral, epidemic typhus vaccine (bacterial); measles, mumps, rubella, live influenza, chickenpox, OPV, rotavirus, yellow fever 17D, hepatitis A, JE (14-14-2 strain) (viral).

Inactivated (Killed) Vaccines

Organisms grown under controlled conditions, then killed by heat or formaldehyde. Safer but less efficacious than live vaccines — requiring larger doses, adjuvants (e.g. alum in DPT), and multiple doses (usually with a booster) to build comparable immunity. Administered subcutaneously or intramuscularly; the only absolute contraindication is a severe reaction to a previous dose.

Examples: typhoid, cholera, pertussis, plague vaccine (bacterial); injectable (Salk) polio, killed influenza, rabies, hepatitis A, JE vaccine (viral).

Toxoid Vaccines

Bacterial exotoxins detoxified (acidic pH, formalin, or prolonged storage) into toxoid — a form that has lost virulence but kept immunogenicity — inducing neutralizing antibody against the toxin itself rather than the organism. Examples: diphtheria toxoid (C. diphtheriae), tetanus toxoid (C. tetani).

Extracted/Cellular Fraction Vaccines

Made from a purified cellular component rather than the whole organism — meningococcal, pneumococcal, and Haemophilus influenzae type b vaccines all use the organism’s capsular polysaccharide.

Subunit Vaccines

Use just the single immunogenic component actually needed for protection — hepatitis B vaccine (hepatitis B surface antigen, HBsAg) and HPV vaccine — typically produced by recombinant DNA technology (the HBsAg gene inserted into baker’s yeast chromosome, which then mass-produces HBsAg as it multiplies).

Combination Vaccines

Combine multiple immunizing agents in one preparation to simplify administration and, sometimes, to boost immunogenicity — in DPT, the pertussis component itself acts as an adjuvant for both diphtheria and tetanus toxoid.

Newer Approaches

DNA vaccines — still experimental — inject small DNA fragments carrying pathogen genes directly; the gene integrates and is transcribed by host cells, which then present the resulting protein to mount an immune response. Edible vaccines — also experimental — transfer the gene for an orally active antigen into a transgenic plant (banana, potato), which then produces the antigen in bulk for direct oral consumption; advantages include low cost, scalability, oral administration, local immunity induction, and heat stability (transgenic potato/tomato against diarrhoeagenic organisms, edible banana against Norwalk virus are current experimental examples).

Cold Chain

The cold chain is the unbroken system of transport, storage, and handling that keeps a vaccine potent from manufacturer to point of administration. Refrigerated vaccines need +2°C to +8°C; frozen vaccines need −15°C or colder; some also need light protection. Broken cold chain is one of the commonest causes of vaccine failure — OPV specifically is the most heat-sensitive vaccine and must be stored at −20°C. Polio and measles vaccines go in the freezer compartment; DPT, TT, Td, BCG, hepatitis B, Hib vaccine, and diluents go in the cold (never frozen) compartment.

The vaccine vial monitor (VVM) is a heat-sensitive label on the vial itself — an outer blue circle (not heat-sensitive, stays blue) and an inner white square that darkens progressively toward blue with cumulative heat exposure. Stage 1 (white) and Stage 2 (light blue) squares mean the vaccine is still usable; Stage 3 (blue, matching the outer circle) and Stage 4 (dark blue) mean discard.

National Immunization Schedule (NIS) 2020

India’s Ministry of Health schedule provides free childhood and pregnancy vaccination. Key elements:

Pregnant women: TT/Td-1 early in pregnancy → TT/Td-2 four weeks later (before 36 weeks) → TT/Td booster if 2 doses were already received within the last 3 years.

Infants: BCG at birth (0.05 mL ID, left upper arm); Hepatitis B birth dose within 24 hours; OPV-0 within 15 days of birth; OPV 1/2/3 and Pentavalent (DPT+Hib+Hepatitis B) 1/2/3 at 6, 10, and 14 weeks; PCV at 6 and 14 weeks with a 9–12-month booster; Rotavirus at 6, 10, 14 weeks; IPV as two fractional intradermal doses at 6 and 14 weeks; Measles/MR 1st dose and JE-1 at 9–12 completed months; Vitamin A 1st dose alongside MR.

Children: DPT booster-1, MR 2nd dose, OPV booster, and JE-2 at 16–24 months; Vitamin A 2nd–9th doses every 6 months to age 5; DPT booster-2 at 5–6 years; TT/Td at 10 and 16 years.

Rotavirus and PCV are currently rolled out only in selected states rather than nationwide.

Passive Immunoprophylaxis (Immunoglobulins)

Ready-made, commercially available immunoglobulin acts immediately, without requiring the recipient’s own immune apparatus to respond — a genuine advantage over vaccination in two situations: immunocompromised individuals who cannot mount their own antibody response, and post-exposure prophylaxis, where immediate protection is needed faster than active immunity could develop. It is also the only option for treating toxin-mediated disease, since antibiotics kill the organism but cannot neutralize toxin already released.

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