T cell responses to SARS-CoV-2 spike cross-recognize Omicron

Abstract

The SARS-CoV-2 Omicron variant (B.1.1.529) has multiple spike protein mutations1,2 that contribute to viral escape from antibody neutralization3–6 and reduce vaccine protection from infection7,8. 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. Here we assessed the ability of T cells to react to Omicron spike protein in participants who were vaccinated with Ad26.CoV2.S or BNT162b2, or unvaccinated convalescent COVID-19 patients (n = 70). Between 70% and 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 for Beta (B.1.351) and Delta (B.1.617.2) variants, despite Omicron harbouring considerably more mutations. In patients who were hospitalized with Omicron infections (n = 19), there were comparable T cell responses to ancestral spike, nucleocapsid and membrane proteins to those in patients hospitalized in previous waves dominated by the ancestral, Beta or Delta variants (n = 49). Thus, despite extensive mutations and reduced susceptibility to neutralizing antibodies of Omicron, the majority of T cell responses induced by vaccination or infection cross-recognize the variant. It remains to be determined whether well-preserved T cell immunity to Omicron contributes to protection from severe COVID-19 and is linked to early clinical observations from South Africa and elsewhere9–12.

SARS-CoV-2 Omicron Symptomatic Infections in Previously Infected or Vaccinated South African Healthcare Workers

“…Although we did not evaluate cell-mediated immunity and immune memory, it has been reported that after natural infection, the T-cell-mediated responses are targeted across a larger variety of epitopes than the humoral response, and therefore, might be more durable to genetic changes in viral epitopes [ 13 ]. Moreover, studies showed that the majority of CD4+ and CD8+ T-cell response to the spike protein induced by vaccination or prior natural infection cross-recognized the Omicron variant, thereby likely contributing to protection against severe disease [ 14 , 15 ]. In addition, Omicron-infected patients had similar T-cell responses to ancestral spike, nucleocapsid, and membrane proteins to those found in patients hospitalized in previous waves [ 15 ].…”

“…Moreover, studies showed that the majority of CD4+ and CD8+ T-cell response to the spike protein induced by vaccination or prior natural infection cross-recognized the Omicron variant, thereby likely contributing to protection against severe disease [ 14 , 15 ]. In addition, Omicron-infected patients had similar T-cell responses to ancestral spike, nucleocapsid, and membrane proteins to those found in patients hospitalized in previous waves [ 15 ].…”

SARS‐CoV‐2 Omicron variant: Immune escape and vaccine development

“…In terms of evasion of cell‐mediated immunity, available information suggests that this immunity induced by vaccines or previous infections remains effective against the Omicron variant. 73 , 74 , 75 However, some mutations, particularly in the ORFs may play a role in immune evasion of the Omicron variant. For example, deletions in ORF1a (L3674, S3675, and G3676) may enhance immune evasion by suppressing viral autophagy.…”

Omicron Genetic and Clinical Peculiarities That May Overturn SARS-CoV-2 Pandemic: A Literature Review

“…Despite the reduced neutralising activity of vaccinated individual sera against the Omicron variant, persistent protection against severe disease might be explained by the fact that vaccine-or infection-induced cellular immunity appears robust against the Omicron variant [79,80]. It is crucial to emphasize that vaccine effectiveness against symptomatic Omicron variant infection, and hospitalisation decreases over time, as stated by numerous studies [4,75].…”