Vaccines: Their Types, Mechanism of action and Schedule

Introduction

In 1796, a British physician named Edward Jenner discovered a ground-breaking concept of preventing a disease. Jenner, curious and determined, decided to test his hypothesis by injecting fluid from cowpox pustules into a young boy. Why cowpox, you ask? Jenner suspected it might prevent the boy from catching the much more severe chickenpox.

To his amazement, Jenner's experiment worked—the boy didn't develop chickenpox. However, Jenner didn't fully understand the mechanism behind this newfound protection. It wasn't until later, when another scientist Louis Pasteur recognized the significance of Jenner's discovery. He coined the term "Vaccine" from the Latin word "Vacca" meaning "cow" in homage to Jenner's discovery. So, through related experimentation the foundation of vaccination as we know it today was laid.

What are Vaccines?

Vaccines are biological preparations of pathogens or their antigens made up of:

· Inactivated (killed) disease-causing organism (virus or bacteria) or

· Attenuated organisms (lost the ability to cause disease) or

· Proteins/toxins/polysaccharides of those organisms.

A particular vaccine mimics an infection upon its injection into the human body. This stimulates and strengthens the immune system against that particular infection (antigen). Vaccines, thus train the immune system to recognize and remember the pathogen, allowing the body to act faster upon its encounter with real pathogen later on. This process involves the activation and development of immune cells, including B cells and T cells, which generate antibodies and initiate cellular immunity, respectively.

Vaccine Types and Their Mechanism of Action

Different types of vaccines are designed to stimulate an immune response against specific pathogens. Here are some common types:

1. Whole organism vaccines: These are of two types

A. Inactivated (killed) vaccines:

The targeted pathogen (disease causing organism) is isolated and cultured in laboratory conditions.

The cultured pathogen has to be killed using different methods such as Heat, Chemicals (e.g. Formaldehyde) or Radiations.

During this process, structure and properties of antigens should not get altered. Heat is the least preferred method as it may denature or spoil the structure of the antigens hence might not be unable to activate the immune system.

Polio vaccines is prepared by using chemical method (formaldehyde)

Inactivated polio virus are injected, intramuscularly or subcutaneously. Immune system recognizes the antigens present on the surface of inactivated pathogen and generates an immune response characterized by the production of antibodies and activation of immune cells (B cells and T cells).

Because the pathogen is not live, these vaccines usually require multiple doses or booster shots to provide sufficient immunity. Examples include the Influenza (flu) vaccine, Hepatitis A vaccine, Rabies vaccine, Polio vaccine etc.

Inactivated (killed ) Vaccine

B. Attenuated Vaccines:

Attenuated vaccines contain live organisms that have been modified to reduce their virulence (disease causing ability) but their antigenic properties remain preserved to stimulate an immune response.

It is mostly done by growing the pathogen in abnormal conditions (e.g. high bile salt concentrations) for prolonged period of time. This causes genetic mutations in the organism.

The selection of mutant involves rigorous testing ensuring reduced virulence, confirmation of their antigenic stability, immunogenicity, and safety profile. This ensure that the attenuated strain is sufficiently weakened not to cause disease but still capable of inducing a strong immune response.

These vaccines provide long-lasting immunity. Examples include the Measles (virus induced rashes in children), mumps (virus causing swelling of salivary glands), Bacillus Calmette-Guerin (BCG) for Tuberculosis and the oral Polio vaccine.

2. Purified Macromolecule as Vaccine

These vaccines include purified and specific parts of the virus or bacteria, such as Proteins, Polysaccharides, or Toxoids (A bacterial toxin weakened until it is no longer toxic) to stimulate an immune response.

Proteins based antigens are more immunogenic due to their structural complexity, diversity of antigenic epitope, better presentation by antigen presenting cells (APC) through MHC to T-cells and effective inducers of immunological memory. Examples include Hepatitis B vaccine and Human papillomavirus (HPV) vaccine.

Toxoid vaccines include inactivated exotoxin of Corynebacterium diphtheriae to prevent disease called Diphtheria involving formation of false membrane in throat causing difficulty in breathing. Tetanus Toxoid vaccine to prevent lockjaw caused by toxins of Clostridium tetani.

Polysaccharide vaccines Certain pathogenic bacteria have capsule composed of polysaccharides such as Pneumonia causing Pneumococcal bacteria. Pneumococcal conjugate Vaccine contains 13 or 23 antigenically different capsular polysaccharides activating B-cells to produce IgM. Examples include vaccines for Hemophilus influenza, Streptococcus pneumoniae.

These vaccines do not contain the pathogens itself, hence are safer for certain populations, such as people with weak immune systems.

3. Viral Vector Vaccines:

These vaccines use a harmless virus (the vector) such as Vaccinia virus (cowpox virus) or Adenovirus. Chosen based on their safety profile, capacity for genetic manipulation, and ability to infect target cells.

The genes encoding “specific antigens” from a pathogenic virus or bacteria are incorporated into the genetic material of the Vector. The vector vaccine containing this modified virus is injected into the human body's cells. The human cells then produce encoded proteins or other components (antigens) of the pathogen, in its natural form without any denaturation or modification triggering an immune response. Examples include the COVID-19 vaccines developed by AstraZeneca (using a chimpanzee adenovirus vector) and Johnson & Johnson (using a human adenovirus vector) incorporated genes encoding spike proteins of the COVID-19 virus.

Vaccine containing Viral Vector with gene encoding “specific antigen”

4. Nucleic acid vaccines:

These vaccines use genetic material, such as DNA or RNA, from the pathogen to stimulate an immune response.

The antigenic genes are cloned into the plasmid (a circular DNA molecule capable of replication and gene expression in host cells). The delivery system mostly includes lipid nanoparticles or viral vectors to protect the genetic material from degradation and facilitate its uptake by host cells.

The genetic material is typically injected either intramuscularly, subcutaneously, or intradermally taken up by cells in the body. Cells then produce proteins (antigens) similar to those of the pathogen, prompting an immune response. mRNA vaccines, like the Pfizer-BioNTech and Moderna encoding the spike proteins of COVID-19 are examples of nucleic acid vaccines.