1. Live Attenuated Vaccines

  • Mechanism: Contain a weakened (attenuated) form of the live virus or bacterium. Must replicate in the host to be effective. Induces a robust and long-lasting humoral and cell-mediated immune response.
  • Key Features:
    • Strong, often lifelong immunity with fewer doses.
    • Risk: Can revert to a virulent form (rare) and may cause disease in immunocompromised individuals.
  • Contraindications: Immunocompromised patients (e.g., HIV with CD4 <200, chemotherapy, SCID) and pregnant women.
  • Examples:
    • Measles, Mumps, Rubella (MMR).
    • Varicella (chickenpox).
    • Rotavirus.
    • Sabin polio vaccine (oral, not used in the US).
    • Yellow fever.
    • Influenza (intranasal).
    • BCG (for TB, not used as a vaccine in the US).

2. Inactivated (Killed) Vaccines

  • Mechanism: Contain whole bacteria or viruses that have been killed by heat or chemicals. The pathogen cannot replicate.
  • Key Features:
    • Induces a primarily humoral (antibody-mediated) immune response.
    • Safer than live vaccines; cannot cause disease.
    • Weaker immune response; often requires boosters.
  • Examples:

3. Subunit, Recombinant, Polysaccharide, and Conjugate Vaccines

  • Mechanism: Contain only specific antigenic components of a pathogen (e.g., proteins, polysaccharides, capsids), not the entire organism.
  • Key Features:
    • Very safe, as they cannot cause disease.
    • May require boosters and adjuvants (substances that enhance the immune response).
  • Types & Examples:
    • Subunit/Recombinant: A piece of the pathogen’s DNA is inserted into a manufacturing cell (like yeast) to produce the antigen.
    • Polysaccharide: Contain the polysaccharide capsule of encapsulated bacteria. Elicits a T-cell-independent immune response, which is weak in infants/young children.
      • Pneumococcal polysaccharide vaccine (PPSV23, Pneumovax).
    • Conjugate: A polysaccharide antigen is chemically linked (conjugated) to a carrier protein. This process converts the immune response to T-cell-dependent, inducing a stronger and more robust response, especially in infants.
      • Haemophilus influenzae type b (Hib).
      • Pneumococcal conjugate vaccine (PCV13, Prevnar).
      • Meningococcal vaccine.

Tip

Why Other Components Are Less Ideal for Vaccines

  • LPS/LOS (Endotoxin):

    • Problem: The Lipid A component is highly toxic and would cause systemic inflammation, fever, and shock if injected as a vaccine. It’s too dangerous.
  • Peptidoglycan:

    • Problem: It is buried underneath other layers (outer membrane in Gram-negatives, thick protein/polysaccharide layers in Gram-positives). Antibodies would not be able to reach it effectively on an intact bacterium. It’s also structurally similar across many bacteria, so it’s less specific.
  • Pili / Fimbriae:

    • Problem: Many bacteria exhibit antigenic variation with their pili—they can rapidly change the pilin proteins to evade the immune system. A vaccine against one type of pilus would quickly become useless. (N. gonorrhoeae is a classic example).
  • Flagella:

    • Problem: Also subject to antigenic variation (phase variation). Not all pathogenic bacteria rely on motility as their primary virulence mechanism.

4. Toxoid Vaccines

  • Mechanism: Contain an inactivated bacterial toxin (toxoid). The immune system develops antibodies against the toxin, not the organism itself.
  • Key Features:
    • Protects against diseases caused by bacterial toxins.
    • Requires boosters.
  • Examples:
    • Clostridium tetani (Tetanus).
    • Corynebacterium diphtheriae (Diphtheria).
    • Included in DTaP, Tdap, and DT vaccines.

5. mRNA Vaccines

  • Mechanism: A lipid nanoparticle delivers mRNA encoding a specific viral antigen (e.g., the spike protein). The host cell’s machinery translates the mRNA to produce the antigen, which then stimulates an immune response.
  • Key Features:
    • Rapid development and production.
    • Induces both humoral and cellular immunity.
    • No risk of infection as it does not contain any live virus. The mRNA does not integrate into the host genome.
  • Examples:
    • COVID-19 (Pfizer-BioNTech, Moderna).

6. Viral Vector Vaccines

  • Mechanism: A modified, harmless virus (the vector, e.g., adenovirus) is used to deliver genetic code for an antigen into host cells, which then produce the antigen to trigger an immune response.
  • Key Features:
    • Generates a strong immune response.
    • Can be developed relatively quickly.
  • Examples:
    • COVID-19 (Johnson & Johnson/Janssen, AstraZeneca).
    • Ebola virus (Ervebo).