Imprinted antibody responses against SARS-CoV-2 Omicron sublineages

Young-Jun Park (1) , Dora Pinto (2) , Alexandra C. Walls (1) , Zhuoming Liu (3) , Anna de Marco (2) , Fabio Benigni (2) , Fabrizia Zatta (2) , Chiara Silacci-Fregni (2) , Jessica Bassi (2) , Kaitlin R. Sprouse (1) , Amin Addetia (1) , John E. Bowen (1) , Cameron Stewart (1) , Martina Giurdanella (2) , Christian Saliba (2) , Barbara Guarino (2) , Michael A. Schmid (2) , Nicholas M. Franko (1) , Jennifer K. Logue (1) , Ha V. Dang (4) , Kevin Hauser (4) , Julia Di Iulio (4) , William Rivera (4) , Gretja Schnell (4) , Anushka Rajesh (4) , Jiayi Zhou (4) , Nisar Farhat (4) , Hannah Kaiser (4) , Martin Montiel-Ruiz (4) , Julia Noack (4) , Florian A. Lempp (4) , Javier Janer (3) , Rana Abdelnabi (5) , Piet Maes (5) , Paolo Ferrari (6, 7, 8) , Alessandro Ceschi (6, 7, 9) , Olivier Giannini (6, 10) , Guilherme Dias de Melo (11) , Lauriane Kergoat (11) , Hervé Bourhy (11) , Johan Neyts (5) , Leah Soriaga (4) , Lisa A. Purcell (4) , Gyorgy Snell (4) , Sean P.J. Whelan (3) , Antonio Lanzavecchia (2) , Herbert W. Virgin (4, 3, 12) , Luca Piccoli (2) , Helen Y. Chu (1) , Matteo Samuele Pizzuto (2) , Davide Corti (2) , David Veesler (1)

1 University of Washington [Seattle]
2 Humabs BioMed SA
3 Washington University School of Medicine [Saint Louis, MO]
4 Vir Biotechnology Inc [San Francisco]
5 KU Leuven - Catholic University of Leuven - Katholieke Universiteit Leuven
6 USI - Università della Svizzera italiana = University of Italian Switzerland
7 Lugano Regional Hospital [Lugano]
8 UNSW - University of New South Wales [Sydney]
9 University hospital of Zurich [Zurich]
10 Bellinzona Regional Hospital [Bellinzona]
11 Lyssavirus, épidémiologie et neuropathologie - Lyssavirus Epidemiology and Neuropathology
12 University of Texas Southwestern Medical Center [Dallas]

Severe acute respiratory syndrome coronavirus 2 (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 elicit plasma neutralizing activity against Omicron BA.1, BA.2, BA.2.12.1 and BA.4/5 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, BA.2, and BA.4/5 receptor-binding domains whereas Omicron primary infections elicit B cells of narrow specificity up to 6 months post 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.

Domains: Life Sciences [q-bio]; Immunology; Life Sciences [q-bio]; Human health and pathology

Young-Jun Park, Dora Pinto, Alexandra C. Walls, Zhuoming Liu, Anna de Marco, et al.. Imprinted antibody responses against SARS-CoV-2 Omicron sublineages. Science, 2022, pp.First release. ⟨10.1126/science.adc9127⟩. ⟨pasteur-03827707⟩