Microbiology 3.7 Notes: The Science of Vaccination
Overview of Vaccination Theory
Theory of Vaccination: A fundamental principle involving the stimulation of immunity against diseases through exposure to comparatively harmless antigens.
Immunity Defined: Resistance to disease caused by microorganisms or the harmful substances they produce.
Types of Immunity:
Sterilizing Immunity: Immunity robust enough to prevent infection; the ultimate goal of vaccination.
Infection Severity and Protective Immunity: An inverse relationship exists between the severity of (corona)virus infection and levels of protective immunity.
Immune Response to Vaccination
Exposure to Antigens: During vaccination, individuals are exposed to microbial antigens which stimulate the immune system.
Primary Immune Response: Part of the response includes the development of immune memory. If an immunized person later encounters the actual pathogen, they will generate a faster and stronger immune response.
Complexity and Challenges of Vaccination
Complex Nature: While the theory of vaccination is straightforward, the reality involves various complexities:
Antigens: Vaccines vary in effectiveness based on their immunogenicity, defined as the ability of antigens to provoke an immune response.
Microbial Evasion: Pathogens have developed sophisticated strategies to evade the immune system, influencing vaccine efficacy.
Vaccine Components
Typical Vaccine Components:
Antigen(s): The actual components that trigger an immune response.
Adjuvants: Molecules added to boost the immunogenicity of the antigens.
Preservatives/Stabilizers: Chemicals that prevent contamination and preserve vaccine integrity.
Antibiotics: Added to prevent bacterial contamination during the production of vaccines.
Vaccine Types Overview
Four main types of vaccines:
Live Attenuated Vaccines.
Inactivated Vaccines.
Subunit (Acellular) Vaccines.
mRNA Vaccines.
1. Live Attenuated Vaccines
Definition: Contain live viruses that have been weakened (attenuated).
Antigens in these vaccines are capable of replication but do not cause disease.
Pros:
Effectively stimulates the immune system, producing robust immunity.
Cons:
Highest risk of adverse effects, and cannot be given to immunocompromised individuals.
Rare instances of vaccine reversion, where the attenuated pathogen regains virulence.
2. Inactivated Vaccines
Definition: Contain pathogens that have been killed or inactivated.
Inactivated by heat, radiation, or chemicals.
Pros:
Lower side effects compared to live vaccines; safer overall.
Cons:
Generally less effective at stimulating a complete immune response.
May require multiple doses for maximum efficacy and lack lifecycle reproduction, limiting immunogenicity.
3. Subunit (Acellular) Vaccines
Definition: Composed of purified components of the pathogen.
These components are typically in a non-infectious form.
Pros:
Fewest side effects; safe for almost all populations.
Cons:
Least immunogenic, necessitating boosters to enhance effectiveness.
4. mRNA Vaccines
Definition: Use messenger RNA to instruct cells to produce the pathogen's proteins, thereby stimulating an immune response.
The mRNA is encapsulated in lipid nanoparticles (LNP) to facilitate entry into cells.
Mechanism:
Once inside, mRNA is translated to produce antigens that are displayed on cell surfaces in Major Histocompatibility Complex (MHC), activating T-cytotoxic, T-helper, and B-cells.
The state is temporary; the injected mRNA degrades after protein synthesis.
Effectiveness:
Initial data indicated that Pfizer-BioNTech and Moderna vaccines showed ≥ 95% effectiveness but declined over time, stabilizing around 55-60% efficacy after two years. Boosters are recommended.
Comparative efficacy: Live-attenuated chickenpox vaccine (95%) vs. inactivated flu vaccines (55-70%).
Serious adverse reaction rates are comparable to existing inactivated vaccines.
Herd Immunity
Concept of Herd Immunity: Not everyone can receive vaccines; thus, a certain percentage of a population must be immunized to prevent disease spread.
General requirement for herd immunity is approximately 85% coverage for most pathogens but can rise to 95% for diseases like measles and pertussis.
Mutation Challenges: Every time a pathogen infects a host, it can mutate, potentially nullifying the achievements of herd immunity.
Case Study: Smallpox
Eradication: Smallpox was declared eradicated by the WHO in 1980, with extensive vaccination efforts contributing to this success.
Vaccine Safety and Effectiveness
Trade-offs: There's always a balance between vaccine safety and effectiveness.
Live-attenuated vaccines are considered the most effective, while subunit vaccines have favorable safety profiles but lower immunogenicity.
Pertussis Vaccine Safety History:
The original pertussis vaccine was whole-cell, leading to several adverse effects, prompting a shift to an acellular version in the 1980s to improve safety.
Encephalitis risk associated with different types of vaccines:
Inactivated vaccine: Incidence counts to be defined.
Subunit vaccine: Incidence counts to be defined.
The switch to a subunit vaccine improved overall vaccine safety.
Current Issues Surrounding Pertussis
Need for Boosters: Subunit vaccines require boosts every ten years, with childhood vaccinations commonly administered as DTaP (Diphtheria, Tetanus, and Pertussis).
Tdap boosts (less diphtheria and pertussis) are often neglected unless individuals suspect tetanus exposure (e.g., from injuries).
Pertussis in Adults: The infection is typically mild. However, as many as 20-30% of adults with chronic cough may harbor this infection.
Vaccine Hesitancy: Combined with the issues above, vaccine hesitancy has contributed to outbreaks, including significant surges in reported infections in years such as 2005, 2011, and 2013.
Measles and Immune Amnesia
Immune Amnesia Defined: Infection with measles virus (MV) causes considerable immune system impairment.
MV primarily infects alveolar macrophages, which migrate to the lymphatic system, transmitting MV to T and B memory cells throughout the body.
Outcomes of Immune Amnesia: Following MV infection, B and T memory cells predominantly recognize only MV, impairing responses to other pathogens.
This significantly increases risks of post-MV complications, injury, and mortality.
Study Guide
Know the basic theory of vaccination.
• Be able to name the four major types of vaccines, know how each is made, and the pros/cons of each.
• Be able to define the terms antigen, stabilizer, and adjuvant and describe the purpose of each in a vaccine.
• Know why there is a trade-off between vaccine safety and vaccine effectiveness
• Be able to describe the trade-off made between safety and effectiveness in Pertussis vaccines made in the 1980s and how that is creating an effectiveness problem today.
• Be able to describe immune amnesia caused by the measles virus
Basic Theory of Vaccination: Involves stimulating immunity against diseases through exposure to harmless antigens.
Four Major Types of Vaccines:
Live Attenuated Vaccines: Contain weakened live viruses; stimulate a robust immune response but have a risk of adverse effects.
Inactivated Vaccines: Contain killed pathogens; safer but generally less effective.
Subunit (Acellular) Vaccines: Composed of purified pathogen components; have the fewest side effects but require boosters for effectiveness.
mRNA Vaccines: Use messenger RNA to instruct cells to make pathogen proteins; initially highly effective but show declining efficacy over time.
Definitions:
Antigen: The component that triggers an immune response.
Stabilizer: Preserves vaccine integrity (e.g., prevents degradation).
Adjuvant: Enhances the immune response to the antigen.
Trade-off Between Vaccine Safety and Effectiveness: Generally, live vaccines are more effective but riskier, whereas subunit vaccines are safer but might not elicit a strong enough immune response.
Pertussis Vaccines Trade-off: The original whole-cell vaccine caused adverse effects, leading to a shift to acellular versions in the 1980s, which improved safety but created effectiveness issues requiring regular boosters.