Host genetic resistance to COVID-19

Division Of Basic Sciences - Nci

Investigators

Linked publications, trials & patents

Abstract

The SARS- CoV-2 Omicron variant (B.1.1.529) was the cause of a new surge of infections globally. With as many as 36 substitutions in the viral spike protein and 59 mutations in total throughout its genome, Omicron has been found to evade neutralization by infection- and vaccine-induced antibodies with unprecedented frequency and escape neutralization by most therapeutic monoclonal antibodies. Additional booster vaccine doses partially compensate for this effect, but the durability of such protective antibody response remains to be determined. Utilizing samples from prior SARS-CoV-2 infected, vaccinated, and both prior infected and vaccinated individuals, it was shown that circulating effector T cell responses and both CD4+ and CD8+ memory T cell responses were generally preserved to the Omicron variant. However, distinct from previous variants of concern (VOCs), such as Delta, a subset of individuals had reduced effector and memory T cell recognition to the Omicron spike protein relative to wild-type spike, with a particularly noticeable effect on spike-specific CD8+ T cell memory re- sponses. Booster doses enhanced the magnitude of responses to wild-type and Omicron spike, although did not completely mitigate the comparatively reduced T cell reactivity to Omicron in individual participants. These findings also raise the prospect that future SARS-CoV-2 variants may variably escape from antibody or T cell responses. They therefore support continued evaluation of second-generation vaccine approaches that induce robust T cell responses that target both variant spike and nonspike antigens in order to overcome current and future SARS-CoV-2 evolution.