Imprinted antibody responses against SARS-CoV-2 Omicron sublineages

Young Jun Park, Dora Pinto, Alexandra C. Walls, Zhuoming Liu, Anna De Marco, Fabio Benigni, Fabrizia Zatta, Chiara Silacci-Fregn, Jessica Bassi, Kaitlin R. Sprouse, Amin Addetia, John E. Bowen, Cameron Stewart, Martina Giurdanella, Christian Saliba, Barbara Guarino, Michael A. Schmid, Nicholas M. Franko, Jennifer K. Logue, Ha V. DangKevin Hauser, Julia Di Iulio, William Rivera, Gretja Schnell, Anushka Rajesh, Jiayi Zhou, Nisar Farhat, Hannah Kaiser, Martin Montiel-Rui, Julia Noack, Florian A. Lempp, Javier Janer, Rana Abdelnabi, Piet Maes, Paolo Ferrari, Alessandro Ceschi, Olivier Giannini, Guilherme Dias De Melo, Lauriane Kergoat, Hervé Bourhy, Johan Neyts, Leah Soriaga, Lisa A. Purcell, Gyorgy Snell, Sean P.J. Whelan, Antonio Lanzavecchia, Herbert W. Virgin, Luca Piccoli, Helen Y. Chu, Matteo Samuele Pizzuto, Davide Corti, David Veesler

Research output: Contribution to journalArticlepeer-review

59 Scopus citations


Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron sublineages carry distinct spike mutations resulting in escape from antibodies induced by previous infection or vaccination. We show that hybrid immunity or vaccine boosters elicit plasma-neutralizing antibodies against Omicron BA.1, BA.2, BA.2.12.1, and BA.4/5, and that breakthrough infections, but not vaccination alone, induce neutralizing antibodies 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, BA.2, and BA.4/5 receptor-binding domains, whereas Omicron primary infections elicit B cells of narrow specificity up to 6 months after infection. Although most clinical antibodies have reduced neutralization of Omicron, we identified an ultrapotent pan-variant-neutralizing antibody that is a strong candidate for clinical development.

Original languageEnglish
Pages (from-to)619-627
Number of pages9
Issue number6620
StatePublished - Nov 11 2022


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