Sumary of SARS-CoV-2 spike mutation L452R evades human immune response and enhances infectivity, researchers find:
- An international team of researchers led by Kumamoto and Tokyo Universities (Japan) have shown that the L452R mutation of the SARS-CoV-2 spike protein, which is common to two mutant strains (Epsilon and Delta), is involved in cellular immunity evasion via the human leukocyte antigen (HLA) A24, and enhances viral infectivity.
- HLA-A24 is one of the most prominent HLA-class I alleles, especially in East/Southeast Asian populations, which might make them particularly vulnerable to coronavirus variants with this mutation.
- Acquired immunity can be broadly classified into humoral immunity mediated by neutralizing antibodies and cellular immunity mediated by helper and killer T cells.
- SARS-CoV-2 “variants of concern,” such as the Alpha and Beta variants, have been studied worldwide for the possibility of humoral immunity evasion.
- In this study, the research group first used immunological experiments to demonstrate that an antigen derived from the SARS-CoV-2 spike protein is strongly recognized by HLA-A24-restricted cellular immunity, which is often found in Japanese people.
- They then performed a large-scale (>750,000) sequence analysis of SARS-CoV-2 strains and found several important mutations in the spike protein region typically recognized by HLA-A24. These are the Y453F spike mutations found in strain B.
- Further immunological experiments demonstrated that these mutations escape HLA-A24 cellular immunity.
- The researchers believe that this is the first time a “variant of concern” has been demonstrated to evade cellular immunity.