New Delhi, 27th Sep. 2022: In a recent study, researchers from the Indian Institute of Technology Madras (IIT Madras) have demonstrated the efficacy of Spike Protein Vaccines against multiple variants of the Coronavirus (SARS COV-2). While further experimental verification is called for, the researchers believe that the present Spike Protein Vaccinations could be effective against circulating variants of SARS COV-2.
This study’s findings 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.
The researchers set out to ascertain what would be the likely response 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. These variations may include the regions of protein sequences recognized by T-cells called epitopes.
Understanding the effect of these variations on the immune response can clarify the efficacy of vaccination against the variants of SARS COV- 2. This computational study has recently been published in the BBA – Molecular Basis of Disease journal.
“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,” says the lead author Dr Vani Janakiraman, Assistant Professor, Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, IIT Madras.
The vaccines could be considered effective against the variants if there are fewer mutated epitopes in their spike proteins and, if the mutated epitopes can still induce an immune response comparable to that of 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.”
“At least 90 per cent of both CD4+ and CD8+ epitopes were found 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 the 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 Janakiraman said.
What is Vaccination?
Vaccination is a process in which a milder form of the virus or a part of it is used to trigger an immune response within 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.
To access the vaccine efficacy, 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.
The Researchers analysed 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.
“Considering that T-dependent responses are a significant correlate of protection via vaccination against viruses, this analysis suggested that broadly conserved CD4+ and CD8+ T cell responses may lead to the retained potential of the present vaccines to fight severity and fatality. Hence, even in the case of reduced neutralization by antibodies, variants may not become vaccine resistant,” the IIT Madras researchers conclude.
(India Science Wire)