Ancestral SARS-CoV-2-specific T cells cross-recognize Omicron (B.1.1.529)

Abstract

The emergence of the SARS-CoV-2 variant-of-concern Omicron (B.1.1.529) has destabilized global efforts to control the impact of COVID-19. Recent data have suggested that B.1.1.529 can readily infect people with naturally acquired or vaccine-induced immunity, facilitated in some cases by viral escape from antibodies that neutralize ancestral SARS-CoV-2. However, severe disease appears to be relatively uncommon in such individuals, highlighting a potential role for other components of the adaptive immune system. We report here that SARS-CoV-2 spike-specific CD4+ and CD8+ T cells induced by prior infection and, more extensively, by mRNA vaccination provide comprehensive heterologous immune reactivity against B.1.1.529. Pairwise comparisons across groups further revealed that SARS-CoV-2 spike-reactive CD4+ and CD8+ T cells exhibited similar functional attributes, memory distributions, and phenotypic traits in response to the ancestral strain or B.1.1.529. Our data indicate that established SARS-CoV-2 spike-specific CD4+ and CD8+ T cell responses, especially after mRNA vaccination, remain largely intact against B.1.1.529.

SARS-CoV-2 Spike-Specific CD4+ T Cell Response Is Conserved Against Variants of Concern, Including Omicron

“…However, when considering the overall response to Spike, we found that the majority of the response is conserved. Our observations are in agreement with works from other groups recently released as pre-print publications, which suggest minimal escape of T cell immunity by Omicron ( 21 – 26 ). Although it may not be sufficient alone to guarantee protection from infection, a conserved CD4+ T cell immunity against common SARS-CoV-2 VOCs may be fundamental to reduce disease severity, as demonstrated by the importance of a rapid T cell response in preventing severe COVID-19 ( 27 ).…”

Mutations of SARS-CoV-2 variants of concern escaping Spike-specific T cells

“…Second, when we tested the combined effect of 30 distinct AA substitutions/deletions (mutations found in Alpha, Beta, Gamma and Delta VOCs, of which 10 have also been detected in Omicron), we found that convalescent or vaccinated individuals of Asian origin possess Spike-specific T cells that largely tolerate the combined AA substitutions. These data agree with the recent reports of the substantial, although not absolute, preservation of global Spike-specific T cell response against the highly mutated Omicron 20–26 .…”

“…We made the unexpected observation that a large number of T cells (20 out of 35) selected in vitro by PBMC stimulation with whole Spike peptide pool recognized peptides carrying the VOC mutated regions of Spike. This is at odds with ex-vivo results obtained by us and others, since T cells specific for variant regions represent a minority of the global Spike T cell repertoire in the ex vivo analysis 7,[18][19][20][21][22][23][24][25][26] . One might speculate that the in vitro expansion mimics the immunological events occurring after SARS-CoV-2 infection and, as such, the analysis of T cells after in vitro expansion selects for the dominant effector T cell response present during the acute phase of response.…”

“…As such, VOC-mutations are unlikely to alter all of them 7,10 . This argument is supported by recent reports documenting the ability of Spike-specific T cells to tolerate the high number of mutations present in Omicron [20][21][22][23][24][25][26] , and likely the immunological basis of why vaccinations are still highly effective against VOCs in reducing severe COVID-19 27 .…”

“…It is made available under a preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in The copyright holder for this this version posted January 25, 2022. ; https://doi.org/10.1101/2022.01. 20.477163 doi: bioRxiv preprint…”