Vaccine development Process

Vaccine: - A substance used to stimulate the production of antibodies and provide immunity against one or several diseases, prepared from the causative agent of a disease, its products, or a synthetic substitute, treated to act as an antigen without inducing the disease.

Vaccine development strategies in case of viral infection

Basically, there are three approaches that we take for vaccine development: -

1)      Traditional Approach

2)      Reverse vaccinology Approach

3)      Structural vaccinology Approach

So, we will discuss them one by one: -

1)      Traditional Approach: - This approach generally includes the traditional methods that is the introduction of attenuated or inactivated infectious agent into the body of a person which helps the immune system to have acquired knowledge about the agent/antigen, so that any further introduction of that antigen into the body would be recognized by the immune system and it produces the required antibody.

This approach has been used against the pathogens causing diseases like mumps, polio, small pox, rubella etc. These are the pathogens having a very low antigen variability (it shows less changes or variation in its antibody binding protein(epitope)).

But this approach is not effective in the cases where the virus shows greater variations to evade the immune system such as HIV, Ebola, Influenza etc.in these cases the vaccine needs to be updated regularly for new strains which is not possible by using the traditional methods.

Introduction of the antigen directly into the body (may be attenuated) creates a risk factor and raises safety concerns.

2)      Reverse vaccinology: - Traditional vaccinology does not required the knowledge of genome sequence but along with time as the technologies like genome sequencing, proteomics etc. have been introduced which have further developed the ways of vaccine development   

Another approach taken for the vaccine development is the reverse vaccinology in which the use of the above-mentioned technologies is done to identify novel candidate immunogen (An immunogen is an antigen or any substance that may be specifically bound by components of the immune system) and surface antigen and analyzed for the antibody binding properties and gene expression profiles. Data is then studied/analyzed to select the most important immunogen.

This immunogen is then taken along with the suitable adjuvant system to develop a vaccine.

 Image Source: - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3696422/bin/nihms-454357-f0001.gif

This approach was used against the following: - Neisseria meningitides, and continuing with Streptococcus pneumonia, pathogenic Escherichia coli, and antibiotic resistant Staphylococcus aureus.

3)      Structural vaccinology approach: -

It goes on by two ways: -

 1) By studying the CD8+ T cells which plays a critical role in clearing the infected cells and controlling the amount of pathogen during a chronic infection but fast antigen variability results in failing of this mechanism. Ideal CD8+ T cells epitopes are located in regions of conserved sequence, where mutation would confer a fitness penalty. So, by using bioinformatic tools the CD8+ T cells epitopes are optimized so that the vaccine can get attached to the CD8+ T cells and it also gets attached to the major histocompatibility complex (MHC).

For example, a composite antigen, termed as mosaic, was assembled to contain conserved T cell epitopes from the HIV-1 gag protein of viral clades B and C. When encoded in an adenoviral vector and delivered to human peripheral blood mononuclear cells, CTL epitopes from both clades were correctly processed and able to induce CTL-mediated cell lysis.

2) By studying the B-cells: - B cells are responsible for generation of specific antibodies for specific antigen. Now this property of B-cells is used to create vaccines which can treat the pathogens with high variability. As we know that there are epitopes which are conserved in an antigen. To these epitopes there are naturally occurring broadly neutralizing antibodies which can identify them, if introduced. So, these epitopes are grafted on the antigen present in the vaccine, which can be identified later when the infectious pathogen attacks.

References: - 

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In my next blog I will write about the possible approach that can be taken to treat COVID-19

By-Curiosityseeker.