ARTICLE OF THE WEEK: LOW DURABILITY OF CONTEMPORARY VACCINES

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Context

• A recently published review of 34 currently licensed vaccines for the duration of their protective immunity reflected that only five vaccines provide long-lasting protection spanning more than 20 years and only three provide lifelong protection.
• Of these 34 vaccines, 15 provide 5-20 years of protection, whereas a similar number of other shots offer short-term protection that lasts around five years or less.

Details

• The differences in the duration of protection provided by different vaccines stem from the complex mechanisms involved in how vaccines induce immune responses.

Factors contributing to varying durations of immunity

Memory B Cells:

• Function: Memory B cells are a crucial component of long-term immunity. They "remember" the antigens introduced by vaccines and trigger a rapid and robust immune response upon re-exposure to the pathogen.
• Role in Immunity: Vaccines that effectively stimulate the production of memory B cells tend to confer longer-lasting protection.
• Examples: Measles and rubella vaccines induce the production of memory B cells that persist for decades, providing lifelong immunity in most cases.

T Cell Response:

• Support for Memory B Cells: T cells play a role in supporting memory B cells' function. Vaccines that stimulate T cell responses alongside B cell responses tend to induce more robust and longer-lasting immunity.
• Importance: Memory B cells require T cell support for optimal function, and vaccines that activate both arms of the immune system typically provide more durable immunity.

Long-Lasting Plasma Cells (LLPCs):

• Function: LLPCs migrate to the bone marrow and can persist for decades, continuously producing antibodies.
• Critical for Lifelong Immunity: Vaccines that generate LLPCs in the bone marrow are more likely to provide lifelong protection.
• Examples: Measles and rubella vaccines are successful in activating LLPCs in the bone marrow, contributing to their long-term effectiveness.

Vaccine-Specific Factors:

• Type of Vaccine: Different types of vaccines (live attenuated, inactivated, subunit, etc.) trigger different immune responses, affecting the duration of protection.
• Persistence of Immune Response: Some vaccines, like the mRNA COVID-19 vaccines, may not effectively activate LLPCs in the bone marrow, potentially leading to shorter durations of protection despite inducing strong initial immune responses.

Mechanism behind the disparity in the duration of vaccine-induced immunity

• It can be explained by various factors falling under three main categories: vaccine-related, target pathogen-related, and host-related.

Vaccine-Related Factors:

• Type of Vaccine: Live viral vaccines, such as those for measles, rubella, yellow fever, chickenpox, and oral polio, often provide longer-lasting protection compared to killed pathogen or subunit vaccines.
• Platform Technology: Newer platforms like virus-like particles (VLPs) can offer long-term protection. For instance, the HPV vaccines were developed using VLP technology.
• Adjuvants: Adding adjuvants to vaccines significantly affects vaccine-induced immune responses and their persistence. Novel adjuvants like Toll-like receptor (TLR) agonists can directly influence memory B cell functions.
• Interval Between Doses: Proper intervals between doses, such as at least six months between priming and booster doses for vaccines like hepatitis B, are crucial for robust and durable immune responses.

Target Pathogen-Related Factors:

• Incubation Period: Viruses with shorter incubation periods, like influenza and SARS-CoV-2, may not provide long-lasting immunity due to the rapid onset of infection, which limits the immune system's response time.
• Type of Infection: Pathogens causing mucosal infections but minimal blood infection, such as SARS-CoV-2 and influenza, can lead to frequent reinfections due to their ability to spread rapidly before the immune response can fully develop.
• Genetic Stability: The genetic stability of the virus contained in a vaccine influences the durability of immunity. RNA viruses like measles and SARS-CoV-2 are known for their high mutation rates, affecting the longevity of vaccine-induced immunity.

Host-Related Factors:

• Age: The individual's age at the time of vaccination influences the persistence of vaccine-induced antibodies, with responses being shorter at extremes of age due to immune system immaturity or senescence.
• Gender: Immune responses may vary with gender, with females generally eliciting more robust immune responses to infections than males.
• Obesity: Recent studies suggest that obesity may accelerate the waning of vaccine efficacy.
• Time of Vaccination: The time of day a vaccine is administered can affect the immune response's robustness, with shots given in the morning showing better immunological responses due to the influence of the circadian clock on immune-cell processes.

What are Vaccines?

• Vaccines are biological preparations that stimulate the immune system to produce immunity to a specific disease, protecting individuals from infection or its severe consequences.
• They typically contain weakened or killed forms of the microorganisms (bacteria or viruses) or their toxins.

Types of Vaccines:

• Live Attenuated Vaccines: These contain weakened forms of the virus or bacteria that are capable of stimulating an immune response without causing illness. Examples include the measles, mumps, and rubella (MMR) vaccine.
• Inactivated Vaccines: These contain killed versions of the virus or bacteria. They often require booster shots because they produce a weaker immune response compared to live vaccines. Examples include the polio vaccine.
• Subunit, Recombinant, Polysaccharide, and Conjugate Vaccines: These contain only specific pieces of the virus or bacteria, such as proteins or sugars, that are necessary to stimulate an immune response. Examples include the hepatitis B vaccine.
• mRNA Vaccines: A newer type of vaccine that uses messenger RNA (mRNA) to instruct cells to produce a protein that triggers an immune response. The mRNA vaccines against COVID-19, such as Pfizer-BioNTech and Moderna, fall into this category.

Vaccine Development Process:

• Preclinical Stage: Researchers conduct laboratory studies and animal testing to identify vaccine candidates and assess their safety and effectiveness.
• Clinical Trials: Vaccines undergo three phases of clinical trials:
  • Phase I: Small-scale trials to evaluate safety and dosage.
  • Phase II: Expanded trials to assess safety, immunogenicity, and dosage.
  • Phase III: Large-scale trials to evaluate efficacy and safety in thousands of participants.
• Regulatory Review: Regulatory agencies review the trial data to assess safety, efficacy, and quality before approving the vaccine for public use.
• Manufacturing and Distribution: Once approved, vaccines are manufactured, distributed, and administered to the public.

Vaccine Administration:

• Vaccination Schedule: Most vaccines require multiple doses administered at specific intervals to ensure adequate immunity.
• Herd Immunity: When a significant portion of the population is vaccinated, it reduces the spread of the disease, protecting those who cannot be vaccinated, such as individuals with weakened immune systems.
• Side Effects: Most vaccines cause only mild side effects, such as soreness at the injection site or low-grade fever. Serious side effects are rare.

Vaccine Misinformation:

• Misconceptions: Misinformation and myths about vaccines can lead to vaccine hesitancy or refusal, reducing vaccination rates and increasing the risk of disease outbreaks.
• Debunking Myths: Scientists and public health experts continuously work to debunk vaccine myths and provide accurate information about the safety and effectiveness of vaccines.

Impact of Vaccines:

• Disease Eradication: Vaccines have led to the eradication of smallpox and near-elimination of diseases like polio and measles in many parts of the world.
• Preventive Healthcare: Vaccines prevent millions of cases of illness, disability, and death each year, saving lives and reducing healthcare costs.

Current Challenges:

• Vaccine Equity: Ensuring equitable access to vaccines remains a challenge, with disparities in vaccine distribution within and between countries.
• Emerging Infectious Diseases: Rapid vaccine development and deployment are crucial in responding to emerging infectious diseases, as demonstrated during the COVID-19 pandemic.

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PRACTICE QUESTION Q.  The duration of vaccine-induced immunity varies based on several factors, including the vaccine's ability to stimulate memory B cells, T cell responses, and the generation of LLPCs in the bone marrow. Comment. (250 Words)