Fundamentals of Vaccine Immunology

Learning Objectives

  • Importance of vaccination programs
  • Types of Vaccines
  • Key vaccine design elements
  • Mechanisms of vaccine-mediated protection:
    • Antigen uptake and presentation
    • Humoral immune responses
    • Cellular immune responses
    • Memory B and T cell responses
  • Correlates of protection
  • Impact of antigen drift and shift on vaccine efficacy

Summary of Vaccines

  • Vaccine: A medical preparation used to protect against diseases.
  • Antigen: A key component that provokes the immune response.
  • Immunogenicity: The ability of a vaccine to provoke an immune response.
  • Efficacy: The measure of how effective a vaccine is under ideal conditions.

Childhood Immunization Schedule

  • Vaccinations typically given at:
    • 2 months: Hepatitis B, DTPa, Hib, etc.
    • 4 months: DTPa, Hib, etc.
    • 6 months: DTPa, Hib, etc.
    • 12 months: MMR, Hib, etc.
    • 18 months: DTPa, Hib, pneumococcal, etc.
    • 4 years: DTPa, polio, etc.

Introduction to Vaccine Immunology

  • Immunology Context:
    • Disease X and its causative agent:
    • Symptoms include fever, cough, pneumonia.
    • Antigens involved are A, B, C.
    • Vaccines aim to trigger an immune response against these antigens.

Overview of Vaccine-Mediated Immune Responses

  • Dendritic cells play a crucial role in presenting antigens to T and B cells.
  • Immune response categories:
    • Humoral: Involves B cells producing antibodies.
    • Cellular: Involves T cells targeting infected cells.

Antigen Presentation and Processing

  • Two main pathways for antigen uptake:
    • Cytosolic (endogenous) pathway: Intracellular pathogens.
    • Endocytic (exogenous) pathway: Extracellular pathogens.
  • Antigen processing leads to peptide presentation with MHC molecules on the cell surface.

T Cell Activation

  • CD4 T cells are activated through antigen presentation.
  • CD4 subsets (e.g., TFH cells) interact with B cells to promote antibody production.

B Cell Activation and Memory Formation

  • B cell response includes:
    • Germinal Center Reaction: Involves somatic hypermutation and class switching.
    • Memory B Cells: Quiescent cells that respond upon re-exposure to antigen.

Role of CD8 T Cells

  • CD8 T effector cells: Critical for response in vaccine-mediated protection.
  • Differentiation into various memory T cell subsets (e.g., central, effector, tissue-resident).

Correlates of Protection (CoP)

  • Immune responses needed for protection from diseases stimulated by vaccines.
  • Types of correlates include:
    • Absolute: Confers near 100% protection.
    • Relative: Usually provides protection but not guaranteed.

Vaccine Design: Key Characteristics

  1. Safety: Suitable for immunocompromised individuals.
  2. Immunogenicity: Induces adequate immune response.
  3. Efficacy: Protects against disease/infection.
  4. Durability: Ensures lasting immune memory.
  5. Manufacturability: Feasibility for large-scale production.
  6. Stability: Long shelf life and ease of storage.

Antigen Drift and Shift

  • Antigenic Drift: Minor mutations leading to reduced antibody binding, allowing evasion.
  • Antigenic Shift: Major changes that can lead to new subtypes and potential pandemics.

Future Vaccination Strategies

  • Development of multi-antigen vaccines targeting various strains (e.g., SARS-CoV-2).