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).