A team of international scientists has recently conducted a mutational analysis of key T cell epitopes of the omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The findings reveal that T cell responses remain significantly strong against the variant.
The study is currently available on the bioRxiv* preprint server, while the article undergoes peer review.
The most recently emerged SARS-CoV-2 variant of concern (VOC) is the omicron variant, which was first detected in South Africa in November 2021. The whole-genome sequencing analysis has suggested that the variant contains several mutations in the key spike epitopes, indicating improved immune fitness. Preliminary studies conducted in real-world pandemic situations have indicated that the variant might potentially escape humoral immune responses induced by infection or vaccination. However, it is still unclear whether the variant is capable of escaping cellular immune responses mediated by T cells.
T cells are vital components of the adaptive immune system. Besides eliminating infected cells, T cells actively participate in activating B cells for antibody production. Robust T cell responses induced by SARS-CoV-2 infection or vaccination have been found to increase viral clearance and reduce disease severity, despite low antibody responses.
In the current study, the scientists have investigated whether omicron mutations affect spike-specific T cell responses induced by infection or vaccination. They have considered all spike-specific CD8+ and CD4+ T cell epitopes of SARS-CoV-2 and screened them against omicron-specific mutations.
The mutational analysis revealed that about 14% of CD8+ T cell epitopes and 28% of CD4+ T cell epitopes contain at least one residue related to an omicron mutation. This finding indicates that most of the T cell epitopes remain unaffected by omicron mutations.
The human leukocyte antigen (HLA) system encodes cell surface molecules that are responsible for presenting antigenic peptide to T cells for viral recognition. In the study, computational modeling was conducted to predict the effects of omicron mutations on the interaction between spike-specific T cell epitopes and their cognate HLA alleles.
The findings revealed that seven CD8+ and 12 CD4+ epitopes were lost due to deletion mutations in the omicron spike protein. Similarly, the mutations caused loss of binding to sixCD8+ and 4 CD4+ epitopes. These observations indicate that most of the T cell epitopes containing omicron mutations retain HLA binding and that there is less possibility of T cell escape.
Non-spike specific T cell responses
The analysis of non-spike specific T cell responses is particularly important as natural infection and inactivated coronavirus disease 2019 (COVID-19) vaccines are known to target T cell epitopes derived from multiple SARS-CoV-2 proteins besides spike protein. In the study, the analysis of all non-spike T cell epitopes revealed that the majority of them are unaffected by omicron mutations. Overall, the mutations caused putative loss of four nucleocapsid-specific T cell epitopes.
Immunodominant T cell epitopes
The analysis of 20 most commonly targeted T cell epitopes (immunodominant epitopes) revealed that omicron mutations are not present in any of these epitopes. Since multiple epitopes are commonly targeted within an individual, these findings suggest that the overall T cell response against the omicron variant remain largely unaffected by mutations.
The study findings reveal that the majority of T cell epitopes targeted in vaccinated or previously infected individuals remain unaffected by omicron mutations. Thus, it can be expected that pre-existing T cell immunity will have a robust impact against the newly emerged omicron variant.
Overall, the study highlights the significance of robust T cell responses in preventing severe omicron infections, despite increased infectivity and antibody escape ability of the variant.
bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.