Immunity in Omicron SARS-CoV-2 breakthrough COVID-19 in vaccinated adults

Author:

Kared Hassen,Wolf Asia-Sophia,Alirezaylavasani Amin,Ravussin Anthony,Solum Guri,Tran Trung The,Lund-Johansen Fridtjof,Vaage John Torgils,Nissen-Meyer Lise Sofie,Nygaard Unni C.,Hungnes Olav,Robertson Anna H,Næss Lisbeth Meyer,Trogstad Lill,Magnus Per,Munthe Ludvig A,Mjaaland Siri

Abstract

AbstractThe new SARS-CoV-2 variant of concern (VOC) Omicron has more than 30 mutations in the receptor binding domain (RBD) of the Spike protein enabling viral escape from antibodies in vaccinated individuals and increased transmissibility1-6. It is unclear how vaccine immunity protects against Omicron infection. Here we show that vaccinated participants at a superspreader event had robust recall response of humoral and pre-existing cellular immunity induced by the vaccines, and an emergentde novoT cell response to non-Spike antigens. We compared cases from a Christmas party where 81 of 110 (74%) developed Omicron breakthrough COVID-197, with Delta breakthrough cases and vaccinated non-infected controls. Omicron cases 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, activated anti-Spike plasmablasts and anti-RBD memory B cells compared to controls. Omicron cases had significantly increasedde novomemory T cell responses to non-Spike viral antigens compared to Delta breakthrough cases demonstrating development of broad immunity. The rapid release of Spike and RBD-specific IgG+B cell plasmablasts and memory B cells into circulation suggested affinity maturation of antibodies and that concerted T and B cell immunity may provide durable broad immunity.

Publisher

Cold Spring Harbor Laboratory

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