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🛡️Immunobiology

Vaccine Types

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Why This Matters

Vaccines represent one of immunology's greatest applications—the deliberate manipulation of adaptive immunity to prevent disease. You're being tested on more than just knowing vaccine names; exams focus on how different vaccine platforms activate the immune system, why certain designs trigger stronger or longer-lasting responses, and which approaches work best for different patient populations. Understanding the mechanisms behind antigen presentation, T cell activation, humoral vs. cellular immunity, and immunological memory will help you predict how each vaccine type performs.

The diversity of vaccine platforms reflects the complexity of pathogens themselves. Some vaccines mimic natural infection closely; others deliver only the minimum antigenic information needed. Each design involves trade-offs between immunogenicity, safety, and practicality. Don't just memorize examples—know what immunological principle each vaccine type demonstrates and why that matters for protection.


Whole-Pathogen Vaccines

These traditional approaches expose the immune system to complete pathogens, either weakened or killed. The more closely a vaccine mimics natural infection, the more robust and diverse the immune response—but with greater safety considerations.

Live Attenuated Vaccines

  • Contain weakened pathogens that replicate without causing disease—this replication amplifies antigen exposure and triggers pattern recognition receptors
  • Stimulate both humoral and cellular immunity—the closest immunological mimic to natural infection, often providing lifelong protection with fewer doses
  • Contraindicated in immunocompromised patients—rare risk of reversion to virulence makes these unsuitable for individuals with weakened immune systems

Inactivated (Killed) Vaccines

  • Pathogens are chemically or heat-killed, eliminating replication capacity and disease risk entirely
  • Primarily stimulate humoral immunity—without replication, MHC Class I presentation is limited, reducing cytotoxic T cell responses
  • Require multiple doses and adjuvants—weaker immunogenicity means boosters are essential for maintaining protective antibody titers

Compare: Live attenuated vs. inactivated vaccines—both use whole pathogens, but live vaccines replicate and trigger robust cellular + humoral immunity, while inactivated vaccines cannot replicate and primarily induce antibody responses. If an FRQ asks about vaccine choice for an immunocompromised patient, inactivated is always safer.


Component-Based Vaccines

Rather than using whole pathogens, these vaccines deliver specific antigenic pieces. This targeted approach minimizes side effects but often requires adjuvants to compensate for reduced immunogenicity.

Subunit Vaccines

  • Contain purified proteins or polysaccharides from the pathogen surface—no genetic material or whole organisms present
  • Highly targeted immune response with excellent safety profile—ideal for patients where reactogenicity is a concern
  • Require adjuvants to enhance immunogenicity—purified antigens alone are poorly recognized by innate immune sensors

Toxoid Vaccines

  • Contain chemically inactivated toxins, training the immune system to neutralize the toxin rather than the pathogen itself
  • Protect against toxin-mediated diseases like tetanus and diphtheria—antibodies block toxin binding to host receptors
  • Require periodic boosters—antibody titers wane over time without the sustained stimulation of replicating antigens

Conjugate Vaccines

  • Link poorly immunogenic polysaccharide antigens to carrier proteins—this recruits T cell help for what would otherwise be a T-independent response
  • Critical for protecting young children—infants cannot mount effective responses to polysaccharide antigens alone due to immature B cell populations
  • Convert T-independent to T-dependent responses—enables class switching, affinity maturation, and immunological memory formation

Compare: Subunit vs. conjugate vaccines—both use pathogen components, but conjugate vaccines specifically address the problem of polysaccharide antigens by adding a protein carrier. This distinction explains why Hib and pneumococcal vaccines work in infants while pure polysaccharide versions don't.


Genetic Vaccines

These modern platforms deliver genetic instructions rather than preformed antigens. Host cells produce the target protein endogenously, enabling MHC Class I presentation and robust cellular immunity.

mRNA Vaccines

  • Deliver messenger RNA encoding pathogen proteins—host ribosomes translate the mRNA, and the protein is processed through normal antigen presentation pathways
  • Stimulate strong humoral and cellular immunity—endogenous protein production enables both MHC Class I and Class II presentation
  • No risk of genomic integration or infection—mRNA is degraded within days and never enters the nucleus

DNA Vaccines

  • Use plasmid DNA to encode pathogen antigens—must enter the nucleus for transcription before translation occurs
  • Largely experimental in humans—challenges with delivery efficiency and immunogenicity have limited clinical applications
  • Offer stability advantages—DNA is more thermostable than mRNA, potentially eliminating cold-chain requirements

Recombinant Vector Vaccines

  • Use harmless viruses to deliver pathogen genetic material—the vector infects cells and expresses the target antigen
  • Induce both humoral and cellular immunity—vector infection triggers innate immune activation while expressed antigens drive adaptive responses
  • Pre-existing vector immunity can limit effectiveness—antibodies against common vectors like adenovirus may neutralize the vaccine before antigen expression occurs

Compare: mRNA vs. DNA vaccines—both deliver genetic instructions, but mRNA works in the cytoplasm while DNA requires nuclear entry. This explains why mRNA vaccines achieved clinical success faster; they bypass the nuclear delivery challenge that has slowed DNA vaccine development.


Quick Reference Table

ConceptBest Examples
Strongest cellular + humoral immunityLive attenuated, mRNA, recombinant vector
Primarily humoral immunityInactivated, subunit, toxoid
Requires adjuvantsInactivated, subunit, toxoid
Safe for immunocompromisedInactivated, subunit, mRNA, toxoid
Targets toxin-mediated diseaseToxoid (tetanus, diphtheria)
Effective in infants for polysaccharidesConjugate (Hib, pneumococcal)
Endogenous antigen productionmRNA, DNA, recombinant vector
Rapid development platformmRNA, recombinant vector

Self-Check Questions

  1. Which two vaccine types produce antigens endogenously within host cells, and why does this matter for the type of immunity generated?

  2. A patient is immunocompromised following chemotherapy. Which vaccine platforms would be contraindicated, and what immunological principle explains this restriction?

  3. Compare and contrast conjugate vaccines and standard subunit vaccines—what specific immunological problem do conjugate vaccines solve, and for which patient population is this most critical?

  4. An FRQ asks you to explain why live attenuated vaccines typically require fewer doses than inactivated vaccines. What mechanisms account for this difference in immunogenicity?

  5. Both mRNA and recombinant vector vaccines emerged as COVID-19 vaccine platforms. What advantage do they share over traditional approaches, and what is one key difference in how they deliver genetic material to host cells?