SARS-CoV-2 spike T cell responses induced upon vaccination or infection remain robust against Omicron

Abstract

The SARS-CoV-2 Omicron variant has multiple Spike (S) protein mutations that contribute to escape from the neutralizing antibody responses, and reducing vaccine protection from infection. The extent to which other components of the adaptive response such as T cells may still target Omicron and contribute to protection from severe outcomes is unknown. We assessed the ability of T cells to react with Omicron spike in participants who were vaccinated with Ad26.CoV2.S or BNT162b2, and in unvaccinated convalescent COVID-19 patients (n = 70). We found that 70-80% of the CD4 and CD8 T cell response to spike was maintained across study groups. Moreover, the magnitude of Omicron cross-reactive T cells was similar to that of the Beta and Delta variants, despite Omicron harbouring considerably more mutations. Additionally, in Omicron-infected hospitalized patients (n = 19), there were comparable T cell responses to ancestral spike, nucleocapsid and membrane proteins to those found in patients hospitalized in previous waves dominated by the ancestral, Beta or Delta variants (n = 49). These results demonstrate that despite Omicron's extensive mutations and reduced susceptibility to neutralizing antibodies, the majority of T cell response, induced by vaccination or natural infection, cross-recognises the variant. Well-preserved T cell immunity to Omicron is likely to contribute to protection from severe COVID-19, supporting early clinical observations from South Africa.

South African Population Immunity and Severe Covid-19 with Omicron Variant

“…Our hypothesis is supported by two recent preprint publications indicating that the majority of the T-cell response induced by vaccination or natural infection cross-recognizes the Omicron variant, thereby likely contributing to protection against severe disease. 20,21 An alternative or additional mechanism by which protection against severe disease may be conferred, despite reduced neutralizing antibody activity against the Omicron variant, is through Fc-mediated effector functions of non-neutralizing antibodies inducing antibody-mediated cellular phagocytosis, complement deposition, and natural killer cell activation. 18,22 In addition, the Omicron variant may be less potent at causing serious illness.…”

“…In particular, the extent to which the polyepitopic T-cell response induced by vaccination against the spike-protein and the even more diverse polyepitopic T-cell response stimulated by natural infection, with or without vaccination, remain cross-reactive against the Omicron variant warrants further investigation. 20,21…”

Omicron infection of vaccinated individuals enhances neutralizing immunity against the Delta variant

“…leads to a lower hospitalization rate with Omicron infection (https://www.discovery.co.za/corporate/health-insights-vaccines-real-world-effectiveness). This may be because Omicron does not have extensive escape from other arms of the adaptive immune response 12 or because Omicron virus shows attenuated cell-to-cell spread 13 which leads to decreased lung infection and pathology 14,15 . A stronger neutralizing response after Omicron infection, as shown here in vaccinated participants, should also contribute to vaccine mediated protection against more severe disease with Omicron.…”

T cell response following anti COVID-19 BNT162b2 vaccination is maintained against the SARS-CoV-2 Omicron B.1.1.529 variant of concern

“…Following antigenic stimulation with the spike-derived peptides, a predominant IFNg response was observed in all the examined individuals, ranging from 50 to 400 secreting cells per 10 6 PBMC, and a lower IL-10 response, ranging from 15 to 82 cells per 10 6 PBMC (figure 1 and 1S). The experimental setup included a 48 hours antigen stimulation step, to allow manifestation of reactivity of IL-4-expressing T cell clones potentially present in the samples, however, almost undetectable levels of IL-4 reactivity was determined, in accordance with previous data pertaining to the responses elicited by the BNT162b2 and m1273 vaccines [2,4,8–13]. Comparison of the average response to the wild type and Omicron spike (Figure 2), indicated only a slight, non-significant decrease, from 201 IFNg-secreting cells following activation with the wild type spike, to 188 cells responding to the Omicron spike.…”