IIT Madras study predicts retained efficacy of spike protein vaccines against Coronavirus variants

New Delhi: Researchers at the Indian Institute of Technology Madras have shown that spike protein vaccines may be effective against multiple variants of the Coronavirus (SARS COV-2).

The results of the IIT Madras study suggest that the attack by selected variants – Delta plus, Gamma, Zeta, Mink and Omicron – may be dealt with by vaccine-induced T-cell responses despite the compromised neutralising antibodies responses.

While further experimental verification is called for, the researchers believe that the present spike protein vaccinations are likely to be efficacious against circulating variants of Coronavirus (SARS COV-2).

The researchers set out to find out what would be the response like if the post-vaccination infections were caused by a variant other than the original Wuhan strain incorporated in vaccine preparations. In variants of SARS COV-2, there are molecular level changes to the spike protein of the virus, and these variations may include the regions of protein sequences that are recognized by T-cells called epitopes.

Understanding the effect of these variations on the immune response can give some clarity about the efficacy of vaccination against the variants of SARS COV- 2.

The Research was led by Dr. Vani Janakiraman, Assistant Professor, Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, IIT Madras.

The results of this computational study have recently been published in the reputed peer-reviewed journal BBA – Molecular Basis of Disease, in a paper co-authored by Mr. S. Sankaranarayanan and Ms. Mugdha Mohkhedkar, Students from the Department of Biotechnology, IIT Madras, and Dr. Vani Janakiraman.

Highlighting the key findings of this research, Dr. Vani Janakiraman, Assistant Professor, Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, IIT Madras, said, “The efficacy of vaccines, in this case, different forms of spike protein based vaccines, depends on whether it can trigger not only the antibody response but also the T cell response. Efficacy against multiple variants can be assessed by first analysing the epitope sequences of various variants for mutations and if they can effectively trigger T-cells induced in the immunization process.”

The vaccines could be considered effective against the variants if there are less mutated epitopes in their spike proteins and, if the mutated epitopes can still induce an immune response comparable to that elicited by original/native epitopes.

Further, Dr. Vani Janakiraman said, “T-cells are an important part of the body’s immune response. T-cells have receptors that bind to the epitope that is presented in conjunction with a large molecule called MHC on the surface of the infected cell.  This triggers the immune response, either afresh or through vaccination memory.”

Vaccination is a process in which, a milder form of the virus or a part of the virus is introduced into the body. Pieces of a protein called epitopes of the injected virus/viral part trigger an immune response in the body.

In the case of spike protein mRNA vaccination, a strand of messenger-RNA is introduced into the host, which teaches the cells to make the      protein, which, in turn, is chopped up into smaller pieces (epitopes) and presented to T-cells. This ultimately triggers the body’s immune response.  In both cases, the response is remembered by the body to guard against future infections.

The IIT Madras team sought to investigate how many of the epitopes in the variants are mutated and whether the mutated epitopes can alter the immune response to vaccination in order to assess the vaccine efficacy.

The researchers analyzed the molecular differences in T-cell epitopes (both CD4+ and CD8+) across a few variants – Delta plus, Gamma, Zeta, Mink and Omicron. These mutated epitope molecular structures were further analysed using immunoinformatics tools to interpret their ability to bind MHC molecules – which can help understand their ability to be recognised by/trigger T cells.

“We found that at least 90 per cent of both CD4+ and CD8+ epitopes were conserved in all the variants except Omicron, but even in Omicron, nearly 75% and 80% of CD4+ and CD8+ epitopes were conserved. Additionally, the immunoinformatics tools also predicted majorly retained ability of the epitopes to bind MHC molecules and hence trigger T cell responses. This means that the changes to the epitopes are       not so large enough to evade the T-cell immune response that the body learned through vaccination,” Dr. Vani Janakiraman said.

Considering that T dependent responses are a major correlate of protection via vaccination against viruses, this analysis suggested that largely conserved CD4+ and CD8+ T cell responses may lead to retained potential of the present vaccines to fight severity and fatality. Hence, even in case of reduced neutralization by antibodies, variants may not become vaccine resistant, the IIT Madras researchers conclude.