Low Durability in Contemporary Vaccines

• Context (TH): Contemporary Vaccines today often display low durability in maintaining protective immunity.
• Recent research conducted a review of 34 licensed vaccines, revealing that only a minority provide prolonged protection exceeding 20 years.

Vaccination

• Vaccines play a crucial role in bolstering our immune system’s defenses against harmful pathogens.
• They aim to mimic natural infections without causing illness.
• Primary immune response: After vaccination, B cells produce antibodies.
• Secondary immune response: Upon re-exposure (boosters or actual pathogen encounter), memory B cells and LLPCs kick into action.

How do the vaccines work?

• Introduction of Antigens:
  • Vaccines contain either weakened or inactivated forms of the pathogen (such as viruses or bacteria) or specific parts of the pathogen (like proteins).
  • When we receive a vaccine, these antigens are introduced into our body.
• Immune System Activation:
  • Our immune system recognizes these antigens as foreign invaders.
  • Specialized cells, such as B cells and T cells, respond to the antigens.
• B Cell Response:
  • B cells produce antibodies—proteins that specifically target the pathogen.
  • These antibodies bind to the antigens, neutralizing them and preventing infection.
• Memory Cells Formation:
  • Some B cells become memory B cells.
  • These memory cells “remember” the pathogen and remain in our system for a long time.
• T Cell Response:
  • T cells play a critical role in coordinating the immune response.
  • They help B cells produce antibodies and directly attack infected cells.

Long-term Immune Protection

• Memory B Cells and Long-Lived Plasma Cells (LLPCs): Memory B cells and LLPCs are key players in long-term immune protection.
  • They form after exposure to a pathogen (or a vaccine) and persist in our body for extended periods.

• Memory B Cells:
  • Function: Memory B cells “remember” specific pathogens.
  • Location: They reside in secondary lymphoid tissues (such as lymph nodes and spleen) and circulate in the blood.
  • Response: When the same pathogen reappears, memory B cells quickly differentiate into plasma cells, producing specific antibodies.
  • Durability: Memory B cells can persist for years or even decades.
• LLPCs:
  • Function: LLPCs are antibody factories.
  • Location: They primarily reside in the bone marrow.
  • Response: When needed, LLPCs churn out antibodies against the pathogen.
  • Durability: LLPCs can survive for a very long time—sometimes a lifetime.

Factors that contribute to the disparity in Vaccine Durability

Vaccine-Related Factors

Vaccine Type

• Live attenuated vaccines (e.g., measles, mumps, rubella):
  • Mimic natural infection closely.
  • Generate robust memory B cells and long-lived plasma cells (LLPCs).
  • Provide long-lasting immunity.
• Inactivated vaccines (e.g., flu shots):
  • May not induce LLPCs as effectively.
  • Require periodic boosters.

Antigen Persistence

• Some vaccines maintain antigen presence longer (e.g., live vaccines).
• Prolonged antigen exposure enhances memory cell formation.

Adjuvants

• Adjuvants (like aluminium salts) enhance immune responses.
• They influence memory cell development.

Route of Administration

• Different routes (intramuscular, oral, nasal) impact immune memory.
• Intramuscular vaccines often generate robust responses.

Target Pathogen-Related Factors

• Pathogen Variation:
  • Some pathogens mutate rapidly (e.g., influenza virus).
  • Antigenic changes require frequent vaccine updates.
• Antigen Complexity:
  • Complex pathogens (e.g., HIV) challenge vaccine design.
  • Generating effective immune memory is difficult.
• Persistence of Pathogen:
  • Some pathogens (e.g., hepatitis B virus) persist in the body.
  • Vaccines must maintain immune memory over time.

Host-Related Factors

• Individual Variation:
  • Genetics, age, health status influence responses.
  • Some individuals mount stronger reactions than others.
• Immunosuppression:
  • Immunosuppressed individuals (e.g., transplant recipients) may have weaker immune memory.
  • Vaccination strategies must consider such populations.

Way Forward

• Develop vaccines that stimulate robust and durable responses.
• Tailor vaccines based on individual factors.
• Design effective booster schedules.
• Boost memory cell responses when needed.
• Address disparities in vaccine access and equity.