Loss of recognition of SARS-CoV-2 B.1.351 variant spike epitopes but overall preservation of T cell immunity

Abstract

SARS-CoV-2 variants have emerged that escape neutralization and potentially impact vaccine efficacy. T cell responses play a role in protection from reinfection and severe disease, but the potential for spike mutations to affect T cell immunity is poorly studied. We assessed both neutralizing antibody and T cell responses in 44 South African COVID-19 patients infected either with B.1.351, now dominant in South Africa, or infected prior to its emergence (first wave), to provide an overall measure of immune evasion. We show for the first time that robust spike-specific CD4 and CD8 T cell responses were detectable in B.1.351-infected patients, similar to first wave patients. Using peptides spanning only the B.1.351 mutated regions, we identified CD4 T cell responses targeting the wild type peptides in 12/22 (54.5%) first wave patients, all of whom failed to recognize corresponding B.1.351-mutated peptides (p=0.0005). However, responses to the mutated regions formed only a small proportion (15.7%) of the overall CD4 response, and few patients (3/44) mounted CD8 responses that targeted the mutated regions. First wave patients showed a 12.7 fold reduction in plasma neutralization of B.1.351. This study shows that despite loss of recognition of immunodominant CD4 epitope(s), overall CD4 and CD8 T cell responses to B.1.351 are preserved. These observations may explain why, despite substantial loss of neutralizing antibody activity against B.1.351, several vaccines have retained the ability to protect against severe COVID-19 disease.

Prior infection with SARS-CoV-2 boosts and broadens Ad26.COV2.S immunogenicity in a variant dependent manner

“…Vaccination induced T cell responses that crossrecognized pooled peptides based on Beta spike, suggesting that most vaccinees target conserved epitopes in spike. These data are in accordance with several recent studies (Reynolds et al, 2021;Gallagher et al, 2021;Geers et al, 2021;Tarke et al, 2021), including our own (Riou et al, 2021b), describing a minimal impact of mutations in SARS-CoV-2 variants on T cell responses in the context of infection and vaccination.…”

Occurrence and significance of Omicron BA.1 infection followed by BA.2 reinfection

“…We observed significantly reduced overall viral load in secondary BA.2 infection samples compared to initial infection together with a lower ratio of subgenomic to genomic RNA. Taken together, this may indicate a more superficial and transient secondary infection that could be explained by T cell-mediated immunity obtained during the first infection 17 . We have previously speculated that infections in the early stage may be associated with the pattern that we see here for the Omicron BA.2 study population 18 , and it is possible that the BA.2 infection in these individuals, happening within a short window after an initial BA.1 infection, may somehow differ, perhaps by being more superficial or transient than the BA.2 infections observed in the randomly selected samples used for comparison.…”

Prior infection with SARS-CoV-2 boosts and broadens Ad26.COV2.S immunogenicity in a variant-dependent manner

“…Vaccination induced T cells that largely cross-recognized peptides based on Beta and Delta spike, suggesting that most vaccinees target conserved epitopes in spike, as previously described (Reynolds et al, 2021;Riou et al, 2021;Gallagher et al, 2021;Geers et al, 2021;Tarke et al, 2021). However, a third of vaccinees showed reduced CD8 recognition of Delta, which harbors the L452R mutation that confers resistance to human leukocyte antigen (HLA)-A*24:02 recognition (Motozono et al, 2021).…”