There have been concerns that several severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have mutations that allow them to evade the immune system. A new study published in the Open Forum Infectious Diseases suggests otherwise. Led by Aaron AR Tobian of Johns Hopkins University School of Medicine, results showed that except for one from the B.1.351 variant, CD8+ T cells showed a broad response to all SARS-CoV-2 variants.
These data highlight the potential significant role of a multi-epitope T cell response in limiting viral escape, and partly mediate protection from disease caused by the SARS-CoV-2 variants,” wrote the researchers. “It will be important to continue to monitor the breadth, magnitude, and durability of the anti-SARS-CoV-2 T cell responses in recovered and vaccinated individuals as part of any assessment to determine if booster vaccinations are needed.”
How they did it
Previous work had found a broad immune response, including CD8+ T cell responses in individuals infected with the original SARS-CoV-2 strain. In this study, they replicated the methods and sought to evaluate CD8+ T cell responses with several coronavirus lineages.
The researchers collected peripheral blood mononuclear cell samples from the convalescent plasma of 30 patients infected with SARS-CoV-2. About 60% of individuals were male, and samples were collected in a median of 42.5 days. They used a multiplex peptide-MHC tetramer staining method to screen for 408 SARS-CoV-2 epitopes that could be potentially recognized by CD8+ T cells. Control samples had CD8+ T cells tested against 20 different peptides of SARS-CoV-2 that were not variants.
The variants of concern — B.1.17, B.1.351, and B.1.1.248 — were found by identifying amino acid polymorphisms unique to them. They were mapped onto the SARS-CoV-2 genome and overlayed with epitopes to study immune responses.
CD8+ T cells recognize SARS-CoV-2 variant epitopes
A total of 132 CD8+ T cells specific to SARS-CoV-2 recognized 52 unique epitopes in the samples.
Only the D80A spike protein mutation found on the third residue of the RFDNPVLPF epitope caused a failure of recognition from the CD8+ T cells. “This is a HLA*A24:02-restricted epitope for which a CD8+ T cell response was detected in one of the five HLA*A24:02+ individuals,” explained the team. This suggests that while there was a low frequency — about 0.005 of total CD8+ T cells-successfully detected this epitope — the frequency of finding this mutation on the epitope is rare. The individual with this particular immune-evading epitope was part of the group with high immunoglobulin G.
SARS-CoV-2 is a virus with many mutations, and while some variants have been detected, others go amiss from inadequate genomic surveillance. The researchers suggest their findings could help with the extent to which a person’s immunity can neutralize variants and prevent transmission of further infection.
It should be noted, that new variants are continuing to be identified all over the world, and it will be important to continually examine these for the possible accumulation of T cell escape mutations,” write the researchers.
The data also emphasizes T cell responses in dealing with the SARS-CoV-2 variant and providing protection. For this reason, vaccines should focus on strengthening T cell responses and neutralizing antibodies and other humoral responses to create an optimal immune response against the variants.
Limitations to consider
While the researchers suggest a broad immune response with CD8+ T cells, the small sample size could have biased the results. Also, all study participants were from North America, with 73% from the United States, and selected for their presence in one or more HLA types.
Given the emergence of new variants around the globe, limiting participants to North America may not be representative of other SARS-CoV-2 infections worldwide. For example, the P.1 variant was not identified in the study but remains a deadly variant of concern in Brazil. The P.1 variant has mutations that allow it to escape the immune system. Future work will need to expand the sample size and test CD8+ T cell response on other circulating variants of concerns to confirm results.