Immunity in Omicron SARS-CoV-2 breakthrough infection in vaccinated adults

ABSTRACT

The new SARS-CoV-2 Omicron variant has more than 15 mutations in the receptor binding domain of the Spike protein enabling increased transmissibility and viral escape from antibodies in vaccinated individuals. It is unclear how vaccine immunity protects against Omicron infection. Here we show that vaccinated participants at a super-spreader event had robust recall response of humoral and pre-existing cellular immunity induced by the vaccines, and an emergent de novo T cell response to non-Spike antigens. Omicron SARS-CoV-2-infected individuals had significantly increased activated SARS-CoV-2 Wild type Spike-specific (vaccine) cytotoxic T cells, activated follicular helper (TFH) cells, functional T cell responses, boosted humoral responses, rapid release of Spike and RBD-specific IgG+ B cell plasmablasts and memory B cells into circulation. Omicron SARS-CoV-2 infected individuals had significantly induced de novo memory T cell responses to non-Spike viral antigens. This concerted T and B cell immunity may provide durable and broad immunity.