Spike Protein Vaccines May Be Effective Against Multiple Variants Of Novel Coronavirus: IIT Madras Study

The study suggests largely conserved T-cell responses across the studied variants, & that T-cells are able to tackle new SARS-CoV-2 variants & aid in protection against Covid-19 following vaccination.

Researchers at the Indian Institute of Technology Madras have shown that spike protein vaccines may be effective against multiple variants of SARS-CoV-2 and that vaccine-induced T-cell responses can deal with the attack by selected variants. These include the Delta plus, Gamma, Zeta, Mink and Omicron variants. 

The researchers believe that the present spike protein vaccinations are likely to be effective against circulating variants of the novel coronavirus, or SARS-CoV-2. However, a drawback is that these vaccines result in compromised neutralising antibody reactions. 

The aim of the study was to find out what the response would be like if a variant other than the wild strain of SARS-CoV-2 is incorporated in vaccine preparations. Molecular changes to the spike protein of SARS-CoV-2 result in different variants of the virus. These variations may include the regions of protein sequences that are recognised by T-cells. These regions are called epitopes (parts of an antigen molecule to which an antibody attaches itself). 

The findings were recently published in the journal BBA - Molecular Basis of Disease. 

What Covid-19 variants were studied?

According to the study, minimal T cell epitopes of SARS-CoV-2 spike protein are mutated in the variants P.1 (Gamma), P.2 (Zeta), B.1.617.2.1 (Delta plus) B.1.1.298 (Mink cluster 5) and B.1.1.529 (Omicron). 

It is important to understand the effect of mutations in variants on the immune response to know about the efficacy of vaccination against these variants. 

When can a spike protein vaccine be considered effective?

According to the study, the spike protein vaccines can be considered effective against the SARS-CoV-2 variants if there are less mutated epitopes in the spike proteins, and if the mutated epitopes can still induce an immune response comparable to that elicited by original epitopes. 

In a statement released by IIT Madras, Dr Vani Janakiraman, one of the authors on the paper, said the efficacy of spike protein vaccines depends on whether it can trigger not only the antibody response but also the T-cell response. He added that 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 in the host organism. 

How do spike protein vaccines trigger an immune response?

Janakiraman said that T-cells are an important part of the body's immune response, and have receptors that bind to the epitope. The epitope is presented on the surface of the infected cell in conjunction with a large molecule called major histocompatibility complex (MHC), which are genes encoding proteins involved in antigen presentation to cells. 

The researcher explained that this triggers the immune response, either afresh or through vaccination memory. 

Spike protein mRNA vaccines introduce a strand of mRNA to the host. This teaches the cells to make the protein which, in turn, is chopped up into smaller pieces called epitopes, and presented to T-cells, ultimately triggering the body's immune response. The body remembers the immune response so that it can guard the organism against future infections. 

The researchers noted in the study that the results of their analysis suggest largely conserved T-cell responses across the studied variants, and that T-cells are able to tackle new SARS-CoV-2 variants and aid in protection against Covid-19 following vaccination.

Therefore, spike protein-based vaccines may not be rendered completely ineffective against new variants, the authors concluded.