Author:
Park Young-Jun,Pinto Dora,Walls Alexandra C.,Liu Zhuoming,De Marco Anna,Benigni Fabio,Zatta Fabrizia,Silacci-Fregni Chiara,Bassi Jessica,Sprouse Kaitlin R.,Addetia Amin,Bowen John E.,Stewart Cameron,Giurdanella Martina,Saliba Christian,Guarino Barbara,Schmid Michael A.,Franko Nicholas,Logue Jennifer,Dang Ha V.,Hauser Kevin,di Iulio Julia,Rivera William,Schnell Gretja,Rajesh Anushka,Zhou Jiayi,Farhat Nisar,Kaiser Hannah,Montiel-Ruiz Martin,Noack Julia,Lempp Florian A.,Janer Javier,Abdelnabi Rana,Maes Piet,Ferrari Paolo,Ceschi Alessandro,Giannini Olivier,Dias de Melo Guilherme,Kergoat Lauriane,Bourhy Hervé,Neyts Johan,Soriaga Leah,Purcell Lisa A.,Snell Gyorgy,Whelan Sean P.J.,Lanzavecchia Antonio,Virgin Herbert W.,Piccoli Luca,Chu Helen,Pizzuto Matteo Samuele,Corti Davide,Veesler David
Abstract
SARS-CoV-2 Omicron sublineages carry distinct spike mutations and represent an antigenic shift resulting in escape from antibodies induced by previous infection or vaccination. We show that hybrid immunity or vaccine boosters result in potent plasma neutralizing activity against Omicron BA.1 and BA.2 and that breakthrough infections, but not vaccination-only, induce neutralizing activity in the nasal mucosa. Consistent with immunological imprinting, most antibodies derived from memory B cells or plasma cells of Omicron breakthrough cases cross-react with the Wuhan-Hu-1, BA.1 and BA.2 receptor-binding domains whereas Omicron primary infections elicit B cells of narrow specificity. While most clinical antibodies have reduced neutralization of Omicron, we identified an ultrapotent pan-variant antibody, that is unaffected by any Omicron lineage spike mutations and is a strong candidate for clinical development.
Publisher
Cold Spring Harbor Laboratory