After the discovery of the vaccine, many researchers tried to produce vaccines for different diseases. One of the major issues of using a vaccine against any disease was seen that in some cases the vaccine which contains the inactivated microbe reverted back after entering the host. There were also vaccine outbreaks, for example: In 1955 when the inactivated poliovirus vaccine (IPV) developed by Jonas Salk was licensed for use against poliomyelitis. Early batches of IPV were not sufficiently inactivated which lead to vaccine-associated outbreaks of polio known as the Cutter incident. So the search for the preparation of a safer vaccine was started by different researchers. In this report, we will briefly understand different types of vaccines and their preparation.  

The classification of vaccine 

  • Different types of vaccine are classified based on which part of the microorganism is used for the preparation of the vaccine
Types of vaccines
Fig: Types of vaccines

1. Whole-Pathogen Vaccines

 Researchers in early age traditionally prepared vaccines that consist of the entire microorganism. The whole microbe was used by either killing or weakening it so that it cannot cause disease. Though these vaccines elicit a very strong immune response some of the vaccines had many side effects.

Edward Jenner injecting attenuated whole pathogen vaccine
Fig: Edward Jenner injecting attenuated whole pathogen vaccine 

It is mainly of two types :

Inactivated or killed vaccine:

Any pathogen after entering the host multiples and cause infection by replicating its genetic material. Researchers thought that if a pathogen replication process is halted by treating it with any chemical, heat, or radiation, but maintaining its property to induce immune response can be used to attain protection. Thus, the inactivated vaccines, are produced by using this technique by killing the pathogen with chemicals, heat, or radiation. The most common chemical used is formalin, it preserves proteins and cellular organelles of the pathogen thereby maintaining the immunogenicity of the pathogen. After immunisation the vaccine antigens cannot replicate (grow) as chemicals like formalin cause changes in the DNA or RNA of the pathogen. These kinds of vaccines also have certain disadvantages. They usually require several doses because the microbes are unable to multiply in the host and so one dose does not give a strong signal to the adaptive immune system. The parts of the pathogen, which are not involved in pathogenicity, may induce the production of antibodies. One of the examples is Havrix, an inactivated vaccine against hepatitis A virus.

Live attenuated vaccine:

These types of vaccines contain a version of the living microbe that has been weakened in the laboratory. It came from the idea of early researchers as they used a milder form of smallpox which causes less severe disease in the recipient which was an early form of ‘attenuation’. There are several approaches to attenuating a  pathogen for use in humans. Preparation of this type of vaccine involves:

  • Growing the virus in a foreign host, for example, measles virus is cultivated in chick egg. Viral replication(growth) in such circumstances alteration of genetic material due to error in a replication which results in the appearance of a number of mutants. Those mutants are then selected as potential vaccine strains since they generally show reduced pathogenicity for the human host and this is a particularly useful approach for RNA viruses that have a high mutation rate. 
  • An alternative approach is to grow the wild virus in an artificial growth medium at a temperature lower than that found in the human body. this technique may lead to emerging of a strain which will grow slowly in human body due to the unavailability of low temperature. Thus, in humans, the adaptive immune responses are able to eliminate it before the virus is able to spread and cause infection. For example, the cold-adapted live attenuated influenza vaccine.

2. Subunit Vaccines

In search of a more safe vaccine lead to the production of subunit vaccines. Unlike whole pathogen vaccines, subunit vaccines do not consist of the entire microorganism but instead include only the components or antigens which activate the immune response. Some of the examples of the subunit vaccine and its preparation:

Splitting of whole virus and using it for subunit vaccine preparation
Fig: Splitting of whole virus and using it for subunit vaccine preparation

Polysaccharide vaccine:

Some microorganisms like bacteria have capsules surrounding their cell, composed of polysaccharide. Researchers used this capsule layer for the preparation of subunit polysaccharide vaccines. Though these types of vaccines are safe it induces a very weak immune response so a protein carrier is used to increase its immunogenicity and such vaccines are known as conjugate vaccines. An example of polysaccharide vaccine is pneumococcal disease vaccine.

Virus like particle  (VLP):

VLPs are prepared from the expression of viral structural proteins that resemble naturally occurring viruses but doesn’t contain the genetic material. Since VLPs cannot replicate in the host it is an ideal immunogen. A VLP can be prepared using single or multiple virus proteins. These type of vaccines activate a similar and strong immune response like the natural virus. An example of the VLP vaccine is the Chikungunya vaccine.

Toxoid vaccine

Certain pathogens cause disease by secreting an exotoxin. Toxoid vaccines use these toxins by altering some components to induce immune response. For example in tetanus, the principal toxin released is called tetanospasmin. 

Tetanus toxoid vaccine is manufactured by growing a highly toxigenic strain of Clostridium tetani in a medium. Bacterial growth and subsequent lysis release the toxin. Later on, formaldehyde treatment converts the toxin to a toxoid by altering particular amino acids and inducing minor molecular conformational changes. The toxoid is physicochemically similar to the native toxin thus inducing cross-reacting antibodies but the changes induced by formaldehyde treatment make it nontoxigenic.

3. Nucleic Acid Vaccines

Another approach of vaccine preparation led to the involvement of genetic material which code for the antigen of the particular microorganism, with the help of the body’s own cells. This technique is helpful in inducing broad long immune responses, so it can be thought of as the future of vaccine preparation. Some of the examples of nucleic acid vaccines are:

DNA plasmid vaccine 

 Preparation of DNA plasmid vaccine
Fig: Preparation of DNA plasmid vaccine

Plasmids are circular extrachromosomal deoxyribonucleic acids present in bacteria naturally. It can be prepared in the laboratory as vectors that code for the proteins from the pathogen of interest after transfer in the host. This type of vaccine is prepared by using expression plasmids which contains expression or transcription unit which allows the transcription of the proteins associated with the pathogen of interest. The plasmids consist of promoter gene which acts as a promoter for transcription of the required viral protein, an origin of replication, and multiple cloning site. DNA plasmids have several advantages including safety, activation of strong immune response and can be easily manufactured. In spite of its advantages, it is still not yet implied in humans. A veterinary DNA vaccine is used to protect horses from the West Nile virus.

mRNA vaccine

 mRNA is the intermediate between DNA and protein formed during the process of transcription. Over a few years, mRNA has become a promising tool in the field of vaccines. The mRNA vaccine is considered to be one of the safest types of the vaccine as it has no potential to cause infection and is degraded by normal cellular processes in the host. The preparation of a mRNA vaccine involves the production of linear DNA using different polymerases such as T7. The mRNA is then engineered which resembles the mRNA molecule produced naturally. The resulting product contains open reading frames, which encode the protein of interest. Cancer mRNA vaccines are prepared to clear or inhibit cancer cells.

Conclusion

The search for an ideal vaccine has led to the advancement of different vaccines, which is helping the society to fight back many diseases. The recent pandemic of COVID19  also has made researchers reuse different vaccine technologies and get a deeper understanding of different vaccines across the globe.

Reference

Baxter, D., 2007. Active and passive immunity, vaccine types, excipients, and licensing. Occupational medicine57(8), pp.552-556.

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