Vaccine science · USMLE

Immunization & vaccine science

Vaccination remains one of the most impactful public health interventions. This guide covers active and passive immunity, vaccine types, special populations, and key organisms — with a USMLE focus.

🛡️ Types of immunity

Active immunity

  • Natural: recovery from infection → memory B/T cells
  • Artificial: vaccination (attenuated, killed, toxoid, subunit, etc.)
  • Long-lasting; provides memory

Passive immunity

  • Natural: maternal IgG across placenta; IgA in colostrum
  • Artificial: antibody preparations (e.g., antivenin, IVIG, monoclonal antibodies)
  • Immediate but temporary; no memory
🧬 Key concept: Primary response: IgM → IgG, 5‑10 days lag. Secondary response: rapid (1‑3 days), high‑affinity IgG, IgA, or IgE due to memory cells.

💉 Vaccine classes

Live attenuated MMR, VZV, rotavirus
Replicate in host, strong humoral + cellular immunity. Contraindicated in immunocompromised. Usually 1‑2 doses.
Killed / inactivated Rabies, IPV, HepA
Chemically inactivated; cannot replicate. Humoral response only; requires boosters.
Toxoid DTaP (diphtheria, tetanus)
Inactivated exotoxins. Prevent disease, not infection. Induce anti‑toxin antibodies.
Polysaccharide PPSV23 (adult)
Pure capsular polysaccharide → T‑cell‑independent (IgM only, no memory).
Conjugate PCV13, Hib, MCV4
Polysaccharide + protein carrier → T‑cell‑dependent; class switching, memory, booster response.
Component (recombinant) HBV, HPV
Immunogenic protein produced in yeast or cell culture. Highly safe, no live component.
⚠️ Contraindication: Live vaccines (MMR, VZV, rotavirus, LAIV) are not given to severely immunocompromised patients (risk of disseminated disease).

Live non‑attenuated vaccine (unique)

Enteric‑coated adenovirus types 4 & 7 (U.S. military) – causes asymptomatic intestinal infection → mucosal IgA memory; protects against aerosol pneumonia.

🧪 Passive immunotherapy

  • Indications: post‑exposure prophylaxis (e.g., rabies, tetanus), snake/spider antivenin, RSV prophylaxis (palivizumab).
  • Risks:
    • Anaphylaxis (IgE against foreign proteins)
    • Serum sickness (type III hypersensitivity) from immune complexes
    • Anti‑allotype responses (even with human Ig)
  • Special consideration: IgA‑deficient patients may react to IgA in IVIG; use IgA‑depleted preparations.
🧪 Humanized monoclonal antibodies (e.g., palivizumab against RSV) are engineered to reduce immunogenicity.

🤱 Maternal antibodies & neonatal immunity

  • IgG crosses placenta (active transport) → protects neonate for first few months.
  • IgM does not cross; detection in newborn indicates congenital infection (e.g., TORCH).
  • IgA in colostrum provides mucosal protection; infant IgA reaches ~20% of adult levels by 12 months.
  • Vaccination timing: Live attenuated vaccines (MMR, VZV) are usually given after 12 months because maternal IgG can neutralize the vaccine virus. If given earlier (high‑risk situations), repeat doses are often needed.
  • Infants with primary immunodeficiencies typically present after maternal IgG wanes (≈3‑6 months).
Maternal IgG Neonatal protection (0‑6 mo) IgG declines Vaccination & own Ig production

🧫 Bacterial vaccines (selected)

OrganismVaccineType
Corynebacterium diphtheriaeDTaP (diphtheria)Toxoid
Clostridium tetaniDTaP (tetanus)Toxoid
Bordetella pertussisDTaP (acellular)Toxoid + filamentous hemagglutinin
Haemophilus influenzae type bHibConjugate (polysaccharide + protein)
Streptococcus pneumoniaePCV13 (pediatric) / PPSV23 (adult)Conjugate (13 serotypes) / Polysaccharide (23 serotypes)
Neisseria meningitidisMCV4Conjugate (serogroups A, C, Y, W‑135)
💡 High yield: Polysaccharide vaccines (PPSV23) induce IgM only and no memory; conjugate vaccines (PCV13) are T‑cell‑dependent → IgG, affinity maturation, and booster response.

🦠 Viral vaccines

VirusVaccineType
RotavirusRV (oral)Live attenuated
PolioIPV (Salk) / OPV (Sabin)Inactivated / Live attenuated
InfluenzaIIV (injected) / LAIV (intranasal)Inactivated / Live attenuated
Varicella zosterVAR (chickenpox) / ZosterLive attenuated
Hepatitis AHepAInactivated
Hepatitis BHepBComponent (recombinant HBsAg)
HPVGardasil 9 (9v)Component (L1 protein)
Measles, Mumps, RubellaMMRLive attenuated
🧬 HPV vaccine: 9‑valent (types 6,11,16,18,31,33,45,52,58) prevents >90% of cervical cancers. Previously quadrivalent (6,11,16,18) covered ~70%.

⭐ High‑yield USMLE facts

🔬 Primary vs secondary response

  • Primary: lag 5‑10 d, low affinity IgM→IgG
  • Secondary: lag 1‑3 d, high affinity IgG/IgA/IgE

🧪 Vaccine type memory

  • Live & conjugate → T‑cell dependent → memory
  • Polysaccharide & toxoid → variable; toxoid induces memory (protein), pure polysaccharide does not
⚠️ Common trap: DTaP contains tetanus and diphtheria toxoids and acellular pertussis components (toxoid + filamentous hemagglutinin) — it is not a live vaccine.
📅 Neonatal vaccination: Live vaccines delayed until >12 months due to maternal IgG interference. Exception: high‑risk exposure, but then boosters are required.
⚠️ Immunocompromised: Avoid live vaccines (MMR, VZV, rotavirus, LAIV, OPV, yellow fever). Killed, toxoid, subunit, and conjugate are generally safe.

✔️ Salk = inactivated polio ✔️ Sabin = live oral polio ✔️ PPSV23 = 23-valent polysaccharide (adult) ✔️ PCV13 = 13-valent conjugate (pediatric)