Science
. 2022 Oct 20;eadc9127.
doi: 10.1126/science.adc9127. Online ahead of print.
Imprinted antibody responses against SARS-CoV-2 Omicron sublineages
Young-Jun Park # 1 2 , Dora Pinto # 3 , Alexandra C Walls # 1 2 , Zhuoming Liu # 4 , Anna De Marco 3 , Fabio Benigni 3 , Fabrizia Zatta 3 , Chiara Silacci-Fregni 3 , Jessica Bassi 3 , Kaitlin R Sprouse 1 , Amin Addetia 1 , John E Bowen 1 , Cameron Stewart 1 , Martina Giurdanella 3 , Christian Saliba 3 , Barbara Guarino 3 , Michael A Schmid 3 , Nicholas M Franko 5 , Jennifer K Logue 5 , Ha V Dang 6 , Kevin Hauser 6 , Julia di Iulio 6 , William Rivera 6 , Gretja Schnell 6 , Anushka Rajesh 6 , Jiayi Zhou 6 , Nisar Farhat 6 , Hannah Kaiser 6 , Martin Montiel-Ruiz 6 , Julia Noack 6 , Florian A Lempp 6 , Javier Janer 4 , Rana Abdelnabi 7 , Piet Maes 7 , Paolo Ferrari 8 9 10 , Alessandro Ceschi 8 11 12 13 , Olivier Giannini 8 14 , Guilherme Dias de Melo 15 , Lauriane Kergoat 15 , Hervé Bourhy 15 , Johan Neyts 7 , Leah Soriaga 6 , Lisa A Purcell 6 , Gyorgy Snell 6 , Sean P J Whelan 4 , Antonio Lanzavecchia 3 , Herbert W Virgin 6 16 17 , Luca Piccoli 3 , Helen Y Chu 5 , Matteo Samuele Pizzuto 3 , Davide Corti 3 , David Veesler 1 2
Affiliations
- PMID: 36264829
- DOI: 10.1126/science.adc9127
Abstract
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.