In order to combat the COVID-19 pandemic, vaccines were produced from the native (Wuhan) SARS CoV-2 strain and were targeted against the spike protein of the virus.
However, with the advent of various mutations of the virus, such as Delta, Omicron, Gamma, and Mink Cluster 5, it became a matter of concern whether the native strains could fight these mutations.
There are two types of immunity – humoral mediated immunity and cell mediated immunity. Usually only the humoral immunity is taken into consideration while producing vaccines. This is because only humoral immunity produces antigen-specific antibodies while cellular immunity does not.
Cellular immunity is governed by what are known as T-cells, which include cells such as CD4+ cells and CD8+ cells. This type of immunity is as important as humoral immunity for eradicating viral infections and other intracellular invaders. CD4+ T-cells assist antibody production and generate long term immune memory.
The T-cell response is activated when the cells recognize epitopes, which are a short segment of proteins that are chopped, mounted on human leukocyte antigen (HLA) and presented to them by a virus infected (via HLA-I) or an antigen presenting cell (via HLA-II).
CD8+ T-cell epitopes are presented via HLA-I, while those CD4+ T-cell epitopes are presented via HLA-II. It is of importance that the binding of the T-cell epitopes to the HLA is crucial for eliciting a T-cell response.
In this study conducted by Mr. S. Sankaranarayanan, Ms. Mugdha Mohkhedkar, and Dr. Vani Janakiraman, from the Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology (IIT) Madras, Chennai, India, bioinformatics studies were performed to analyze the spike protein T-cell epitope repertoire and their human leukocyte antigen (HLA) binding patterns in native and mutant strains of SARS CoV-2 to gain insight into potential variation in T-cell responses against new variants. This would indicate whether the new variants escape the cell mediated immunity induced by spike protein vaccines.
It was found that nearly 90 percent CD4+ and CD8+ epitopes across Delta Plus, Gamma, Zeta, and Mink Cluster 5 variants were conserved. Nearly 75 percent CD4+ and nearly 87 percent CD8+ epitopes were conserved in the Omicron variant.
The analysis suggest that the T-cell responses across the variants were likely largely conserved and so are capable of tackling new SARS CoV-2 variants and aid in protection from COVID-19 post vaccination.
Dr. Girdhari Lal, from National Centre for Cell Science (NCCS), Pune, India, pointed out the importance of this study by giving the following comments: “Dr. Janakiraman and her team used a bioinformatic approach to look into the alteration in the SARS-CoV2 spike protein for the potential T cell epitope to induce a protective immune response in humans. This is a fascinating study, where her team showed that across the various variants of the SARS-CoV2 virus, the majority of CD4 and CD8 T cell epitopes were not mutated much and were able to bind several HLA they tested. They concluded that vaccination strategies currently used might retain the T cell immunity in vaccinated individuals, and these conserved reasons may form a potential better vaccine candidate to control COVID-19 infection”
Article by Akshay Anantharaman
Here is the original link to the paper:
https://www.sciencedirect.com/science/article/pii/S0925443922001028
