Preparation and standardisation of vaccines and immunization

Table of contents

Preparation and Standardization of Vaccines and Immunization Schedules

Vaccines are one of the most critical tools in public health, preventing millions of deaths each year.
Vaccine development is a complex and rigorous process that involves identifying effective antigens, ensuring vaccine safety and efficacy, and developing protocols to standardize their production and administration.
Immunization schedules are equally important, as they guide the timing of vaccine doses to optimize immunity in individuals and populations.
This document provides a detailed overview of vaccine preparation, standardization, and the development of immunization schedules.

I. Preparation of Vaccines

The vaccine preparation process involves multiple stages to ensure that vaccines are safe, effective, and consistently manufactured.

1. Vaccine Development Phases

Exploratory Phase: During this phase, researchers identify potential antigens, such as proteins or polysaccharides, that could trigger an immune response. Antigen selection focuses on components of a pathogen that are essential for its infection process, such as surface proteins or toxins. This stage is primarily done in laboratory settings to understand the pathogen’s structure and its interaction with the immune system.
Preclinical Testing: Animal studies are conducted to evaluate the safety and immunogenicity of the candidate vaccine. This phase involves immunizing animal models, such as mice or monkeys, to determine the immune response and assess potential adverse effects. Researchers also test vaccine dosage, route of administration, and formulation in these animal models to predict efficacy and safety in humans.
Clinical Trials:

- Phase I: Conducted on a small group (20-80) of human volunteers to evaluate basic safety, tolerability, and dose-response relationships.
- Phase II: This involves a larger group (several hundred) further to test efficacy in terms of immune response and safety. The immune responses in different demographic groups, including age, gender, and health status, are examined.
- Phase III: Large-scale trials with thousands of participants are conducted to confirm efficacy and monitor for rare side effects. This phase also assesses how well the vaccine protects against infection in diverse populations.

Regulatory Review and Approval: Regulatory bodies, such as the FDA or WHO, conduct rigorous reviews of clinical trial data to confirm that the vaccine meets safety and efficacy standards before approval.
Phase IV (Post-Marketing Surveillance): After approval, the vaccine continues to be monitored to identify rare side effects and ensure long-term safety.

2. Types of Vaccines

Vaccines are designed based on the biological characteristics of the pathogen and include:

Inactivated or Killed Vaccines: These vaccines contain pathogens that have been killed or inactivated using heat or chemicals, such as formaldehyde. They can’t replicate in the host but can still stimulate an immune response, as seen with the inactivated polio vaccine (IPV).
Live Attenuated Vaccines: These vaccines contain a weakened form of the pathogen that can replicate but typically does not cause illness. Examples include MMR and varicella vaccines. Attenuation is achieved by altering the pathogen’s genetic material or growing it in laboratory conditions, reducing its ability to cause disease.
Subunit, Recombinant, and Conjugate Vaccines: These vaccines include only specific antigens from the pathogen, such as proteins or polysaccharides, rather than the entire pathogen. Conjugate vaccines, like the Haemophilus influenzae type b (Hib) vaccine, link polysaccharides to a protein to enhance infant immunogenicity.
Toxoid Vaccines: Created for pathogens where the toxin, rather than the pathogen itself, causes disease. Examples include the diphtheria and tetanus vaccines, which contain inactivated toxins that stimulate immunity against these specific toxins.
mRNA Vaccines: These use mRNA to instruct cells to produce pathogen-specific proteins. Pfizer and Moderna COVID-19 vaccines are examples, using mRNA to produce the SARS-CoV-2 spike protein in host cells, thereby triggering an immune response.
Viral Vector Vaccines: These use a modified virus (not the disease-causing virus) to deliver genetic material from the target pathogen. An example is the Johnson & Johnson COVID-19 vaccine, which uses an adenovirus vector to carry the SARS-CoV-2 spike protein gene.

3. Production Process

Antigen Production: Antigens, the active components that elicit immunity, are produced depending on the type of vaccine. The virus or bacteria is grown in conditions that weaken it for live-attenuated vaccines. For protein-based vaccines, cells may be engineered to produce the desired protein.
Purification: Antigens are separated and purified to remove impurities, ensuring the safety and potency of the vaccine.
Addition of Adjuvants: Adjuvants enhance immune response, especially for inactivated or subunit vaccines. Aluminum salts, like aluminum hydroxide, are commonly used adjuvants in vaccines like hepatitis B.
Formulation: The purified antigen and other ingredients (such as stabilizers or preservatives) are combined to form the final vaccine. Stabilizers, such as sugars and amino acids, are added to protect vaccine integrity during storage.
Filling and Packaging: Under sterile conditions, the vaccine is filled into vials, ampoules, or prefilled syringes. Each vial must be labeled with a batch number for tracking.
Quality Control: Each batch undergoes testing for safety, sterility, and consistency to ensure uniformity. This involves testing in compliance with WHO and GMP (Good Manufacturing Practices) standards.

II. Standardization of Vaccines

Standardization is key to ensuring that vaccines meet rigorous safety and efficacy standards. Regulatory agencies like the WHO and FDA have established protocols for ensuring batch consistency and quality control.

1. Quality Control and GMP

Good Manufacturing Practices (GMP): Vaccine manufacturers must adhere to GMP, which involves strict guidelines on facilities, equipment, and personnel involved in production to avoid contamination and ensure high standards.
Potency and Efficacy Testing: Each batch of the vaccine is tested for potency by measuring the immune response in laboratory animals or in cell-based assays.
Sterility Testing: Testing for contaminants such as bacteria, fungi, or other microorganisms is performed to prevent infections in vaccine recipients.

2. Regulatory Approval

WHO Prequalification: WHO’s prequalification process is especially important for vaccines used internationally, ensuring that vaccines meet global standards.
Cold Chain Requirements: Some vaccines need to be stored at specific temperatures. Cold chain requirements ensure that vaccines remain effective from manufacturing to administration.

III. Immunization Schedules

Immunization schedules specify the timing and sequence of vaccines to optimize protection. National health authorities and organizations like WHO and CDC create schedules based on scientific evidence.

1. Factors Influencing Immunization Schedules

Age-Related Immunity: Infants, children, and older adults have different immune responses. Certain vaccines are more effective at specific ages, and maternal antibodies can interfere with some vaccines if given too early.
Disease Epidemiology: Immunization schedules consider the prevalence and risk of infectious diseases in a particular region.
Vaccine Type: Vaccines requiring boosters (e.g., tetanus) are scheduled accordingly to maintain immunity.
Population Needs: Healthcare workers, pregnant women, and those traveling to endemic areas may require additional vaccines.

2. Typical Immunization Schedules

Infants and Children:

- Birth: Hepatitis B and BCG for tuberculosis in high-prevalence areas.
- 2, 4, and 6 Months: DTaP, Hib, polio, and hepatitis B.
- 12-15 Months: MMR, varicella, and pneumococcal conjugate vaccine (PCV).
- 4-6 Years: Boosters for DTaP, MMR, and polio.

Adolescents:

- HPV vaccines are typically given at ages 11-12.
- Meningococcal vaccine for protection against meningitis.

Adults and High-Risk Groups:

- Tetanus and diphtheria boosters every 10 years.
- Influenza and pneumococcal vaccines for older adults.
- Special immunizations for travelers, such as yellow fever.

3. Considerations for Immunization Schedules

Catch-Up Schedules: For those who missed doses, catch-up schedules provide a means to ensure immunity is acquired later in life.
Immunocompromised Individuals: Live vaccines are often avoided; special schedules may be created to minimize health risks.

IV. Challenges in Vaccine Implementation

Cold Chain Management: Maintaining the cold chain for vaccines is essential but challenging in regions with limited resources.
Vaccine Hesitancy: Vaccine misinformation and fear can delay or reduce immunization coverage, leading to outbreaks.
Global Health Disparities: Access to vaccines is often unequal, with low-income countries facing supply and funding issues.