Preserved T cell reactivity to the SARS-CoV-2 Omicron variant indicates continued protection in vaccinated individuals

Abstract

Importance: The emergence of the highly contagious Omicron variant of SARS-CoV-2 and the findings of a significantly reduced neutralizing potency of sera from convalescent or vaccinated individuals imposes the study of cellular immunity to predict the degree of immune protection to the yet again new coronavirus. Design: Prospective monocentric observational study. Setting: Conducted between December 20-21 at the Santa Lucia Foundation IRCCS. Participants: 61 volunteers (Mean age 41.62, range 21-62; 38F/23M) with different vaccination and SARS-CoV-2 infection backgrounds donated 15 ml of blood. Of these donors, one had recently completed chemotherapy, and one was undergoing treatment with monoclonal antibodies; the others reported no known health issue. Main Outcome(s) and Measure(s): The outcomes were the measurement of T cell reactivity to the mutated regions of the Spike protein of the Omicron SARS-CoV-2 variant and the assessment of remaining T cell immunity to the spike protein by stimulation with peptide libraries. Results: Lymphocytes from freshly drawn blood samples were isolated and immediately tested for reactivity to the Spike protein of SARS-CoV-2. T cell responses to peptides covering the mutated regions in the Omicron variant were decreased by over 47% compared to the same regions of the ancestral vaccine strain. However, overall reactivity to the peptide library of the full-length protein was largely maintained (estimated 83%). No significant differences in loss of immune recognition were identified between groups of donors with different vaccination and/or infection histories. Conclusions and Relevance: We conclude that despite the mutations in the Spike protein, the SARS-CoV-2 Omicron variant is nonetheless recognized by the cellular component of the immune system. It is reasonable to assume that protection from hospitalization and severe disease is maintained.

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 Spikespecific 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][21][22][23][24][25][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 .…”

Immunogenicity and reactogenicity of SARS-CoV-2 mRNA and inactivated vaccines in healthy adolescents

“…52 In contrast, several studies found that T cell responses against the Omicron S protein are largely preserved (>80%) in most vaccinated and previously infected adults. 48,[53][54][55][56][57] This lasting cellular immunity is one of many possibilities that contributes to the high (70%) clinical effectiveness of 2 doses of BNT162b2 doses against hospitalization during the initial Omicron wave. 58 Since this study showed that vaccine-induced T cell responses in adolescents are similar to adults, it is likely that their T cell responses remain protective against VOCs, including Omicron.…”

Durability of BNT162b2 vaccine against hospital and emergency department admissions due to the omicron and delta variants in a large health system in the USA: a test-negative case–control study

“…3 , 4 , 5 , 6 , 7 However, early data suggest that T-cell responses induced by previous SARS-CoV-2 infection and by the BNT162b2 vaccine are not significantly altered against omicron. 8 , 9 , 10 , 11 , 12 Although these findings suggest that protection against severe SARS-CoV-2 infection with omicron is likely to be better preserved than that against less symptomatic infection in most individuals, the extent of the impact on vaccine effectiveness and potential waning is unclear.…”