August 11, 2022

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T-cell vaccine can provide extensive protection against COVID-19 mutantions

Cell: T-cell vaccine can provide extensive protection against COVID-19 mutantions and related viruses


T-cell vaccine can provide extensive protection against COVID-19 mutantions.  The rapid spread of the COVID-19 epidemic on a global scale has provided ample opportunities for the emergence of COVID-19 virus mutations.

This mutation site that allows the virus to evade the immune response is called a mutant epitope. The emergence of mutant strains makes people urgently need to develop new vaccines.

Neutralizing antibodies are a key component of vaccines, but induction of virus-specific CD8+ T cells can greatly enhance the protective effect of antibodies. In addition, CD8+ T cells can attack the entire region of the SARS-CoV-2 proteome, so they can target mutation-restricted epitopes.

The so-called mutation-restricted epitope can be understood as a load-bearing wall. A virus is a house. The virus can change windows and doors (mutated epitopes), but it cannot change the load-bearing wall (mutation-restricted epitopes). These mutation-restricted epitopes are different. Among the virus variants, even among viruses of the same family, they are usually almost the same, which makes them ideal vaccine targets. Therefore, identifying the mutation-restricted epitope of the virus is crucial for the development of new vaccines.

Recently, the research team of MIT and Harvard University published a research paper titled: Structure-guided T cell vaccine design for SARS-CoV-2 variants and sarbecoviruses in the world’s top academic journal Cell.

The study identified SARS-CoV-2 epitopes with limited mutations through structure-based network analysis. These epitopes are not prone to mutations and are recognized by T cells. Using these epitopes, vaccines can be developed to train T cells and provide protective immunity. This work highlights the possibility of developing a T-cell vaccine that can provide extensive protection against new variants of SARS-CoV-2 and other SARS-like coronaviruses.

In order to determine the mutation-restricted regions in the SARS-CoV-2 proteome, the research team applied structure-based network analysis and the evaluation of the stability of HLA class I peptides to define the mutation-restricted CD8+T in the SARS-CoV-2 proteome. Cell epitope.

The results show that highly networked epitopes are conserved in cyclic mutations and the entire SARBE virus subgenus, and when mutated, they disproportionately damage the infectivity of the virus.

It has been more than a year since the COVID-19 pandemic. If their prediction of SARS-CoV-2 is correct, then the variant strain should have almost no mutations in the highly networked epitope they identified.

So they compared the sequence at that time with the newly popular B.1.1.7 (Alpha), B.1.351 (Beta), P1 (Gamma) and B.1.617.2 (Delta) SARS-CoV-2 variant sequences and found The vast majority of new sequence mutations in SARS-CoV-2 appeared in non-networked regions, which confirmed their prediction.

Next, the research team evaluated the HLA class I stabilizing activity of 18 globally circulating alleles in circulating SARS-CoV-2 variants and deep-sequenced main isolates to determine CD8 in a highly networked region with limited mutation frequency. + T cell epitope.

Importantly, these epitopes cause obvious CD8+ T cell reactivity in individuals recovering from COVID-19, while individuals vaccinated with mRNA vaccines have much less response to T cells with highly networked epitopes.

In general, the study clarified the key mutation-restricted regions and immunogenic epitopes in the SARS-CoV-2 proteome. These epitopes are structurally restricted by mutations and are conserved in new coronavirus variants and sarbecoviruses. , And was recognized by individual T cells recovered from COVID-19. These results provide a basis for the rational development of global T cell vaccines against the newly emerging SARS-CoV-2 variants and future SARS-like coronaviruses.




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