Assessment of T-cell Reactivity to the SARS-CoV-2 Omicron Variant by Immunized Individuals

Abstract

IMPORTANCEThe emergence of the highly contagious Omicron variant of SARS-CoV-2 and the findings of a significantly reduced neutralizing potency of sera from individuals with previous SARS-CoV-2 infection or vaccination highlights the importance of studying cellular immunity to estimate the degree of immune protection to the new SARS-CoV-2 variant. OBJECTIVE To determine T-cell reactivity to the Omicron variant in individuals with established (natural and/or vaccine-induced) immunity to SARS-CoV-2. DESIGN, SETTING, AND PARTICIPANTS This was a cohort study conducted between December 20 and 21, 2021, at the Santa Lucia Foundation Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy, among health care worker and scientist volunteers. Lymphocytes from freshly drawn blood samples were isolated and immediately tested for reactivity to the spike protein of SARS-CoV-2. MAIN OUTCOMES AND MEASURES The main outcomes were the measurement of T-cell reactivity to the mutated regions of the spike protein of the Omicron BA.1 SARS-CoV-2 variant and the assessment of remaining T-cell immunity to the spike protein by stimulation with peptide libraries. RESULTS A total of 61 volunteers (mean (range) age, 41.62 (21-62) years; 38 women [62%]) with different vaccination and SARS-CoV-2 infection backgrounds were enrolled. The median (range)frequency of CD4 + T cells reactive to peptides covering the mutated regions in the Omicron variant was 0.039% (0%-2.356%), a decrease of 64% compared with the frequency of CD4 + cells specific for the same regions of the ancestral strain (0.109% [0%-2.376%]). Within CD8 + T cells, a median (range) of 0.02% (0%-0.689%) of cells recognized the mutated spike regions, while 0.039% (0%-3.57%) of cells were reactive to the equivalent unmutated regions, a reduction of 49%.However, overall reactivity to the peptide library of the full-length protein was largely maintained (estimated 87%). No significant differences in loss of immune recognition were identified between groups of participants with different vaccination or infection histories. CONCLUSIONS AND RELEVANCEThis cohort study of immunized adults in Italy found that despite the mutations in the spike protein, the SARS-CoV-2 Omicron variant was recognized by the cellular component of the immune system. It is reasonable to assume that protection from hospitalization and severe disease will be maintained.

Heterologous vector versus homologous mRNA COVID-19 booster vaccination in non-seroconverted immunosuppressed patients: a randomized controlled trial

“…In our study, T-cell responses to spike peptide pools from Wuhan and Omicron variants showed largely comparable results. This is in line with recent data reporting that the cellular response to SARS-CoV-2 variants is preserved in most infected and vaccinated individuals 43 – 47 . As T-cell responses to SARS-CoV-2 spike peptides could be influenced by pre-existing cross-reactive immunity against other human corona viruses 48 , 49 , we analyzed responses to the more variable S1 part containing the RBD and more conserved membrane-proximal S2 moiety of the spike protein separately.…”

Immunogenicity and reactogenicity of SARS-CoV-2 vaccines BNT162b2 and CoronaVac in healthy adolescents

“…Moreover, despite exponential differences in neutralising antibody titres, SARS-CoV-2 vaccines of different platforms including mRNA, adenoviral vector and inactivated vaccines have been shown to produce potent T cell responses and very high effectiveness against hospitalisation 31,[47][48][49] . Multiple lines of evidence support the contention that T cells play a major role in mediating protection against severe COVID-19 31,[49][50][51][52][53][54][55][56] . Therefore, our T cell results suggest adolescents receiving either vaccine are also protected from severe COVID-19.…”

“…against the Omicron S protein are largely preserved (>80%) in most vaccinated and previously infected adults 49,[51][52][53][54][55] . This lasting cellular immunity is one of many possibilities that contributes to the high clinical effectiveness of 2 doses of BNT162b2 doses against hospitalisation and death during the initial Omicron wave [64][65][66][67][68] .…”

Increased Secondary Attack Rates among the Household Contacts of Patients with the Omicron Variant of the Coronavirus Disease 2019 in Japan

“…Released IFN-γ was significantly reduced when cells were incubated with the peptide compared with those of the ancestral strain. However, the overall reactivity to the peptide library of the full-length protein was largely maintained [36]. SARS-CoV-2-specific T cells were detected up to 6 months after all vaccination, and no significant differences were detected between WT-and variant-specific CD4+ or CD8+ T cell responses, including omicron [37].…”