Imprinted antibody responses against SARS-CoV-2 Omicron sublineages

Author:

Park Young-Jun12ORCID,Pinto Dora3,Walls Alexandra C.12ORCID,Liu Zhuoming4ORCID,De Marco Anna3ORCID,Benigni Fabio3ORCID,Zatta Fabrizia3ORCID,Silacci-Fregni Chiara3,Bassi Jessica3ORCID,Sprouse Kaitlin R.1ORCID,Addetia Amin1ORCID,Bowen John E.1ORCID,Stewart Cameron1ORCID,Giurdanella Martina3,Saliba Christian3ORCID,Guarino Barbara3ORCID,Schmid Michael A.3ORCID,Franko Nicholas M.5ORCID,Logue Jennifer K.5ORCID,Dang Ha V.6ORCID,Hauser Kevin6,di Iulio Julia6ORCID,Rivera William6,Schnell Gretja6,Rajesh Anushka6,Zhou Jiayi6ORCID,Farhat Nisar6ORCID,Kaiser Hannah6ORCID,Montiel-Ruiz Martin6ORCID,Noack Julia6ORCID,Lempp Florian A.6ORCID,Janer Javier4ORCID,Abdelnabi Rana7ORCID,Maes Piet7ORCID,Ferrari Paolo8910ORCID,Ceschi Alessandro8111213ORCID,Giannini Olivier814ORCID,de Melo Guilherme Dias15ORCID,Kergoat Lauriane15ORCID,Bourhy Hervé15ORCID,Neyts Johan7ORCID,Soriaga Leah6ORCID,Purcell Lisa A.6ORCID,Snell Gyorgy6ORCID,Whelan Sean P. J.4ORCID,Lanzavecchia Antonio3ORCID,Virgin Herbert W.61617ORCID,Piccoli Luca3ORCID,Chu Helen Y.5ORCID,Pizzuto Matteo Samuele3ORCID,Corti Davide3ORCID,Veesler David12ORCID

Affiliation:

1. Department of Biochemistry, University of Washington, Seattle, WA, USA.

2. Howard Hughes Medical Institute, University of Washington, Seattle, WA, USA.

3. Humabs Biomed SA, Subsidiary of Vir Biotechnology, Bellinzona, Switzerland.

4. Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA.

5. Division of Allergy and Infectious Diseases, University of Washington, Seattle, WA, USA.

6. Vir Biotechnology, San Francisco, CA, USA.

7. KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, B-3000 Leuven, Belgium.

8. Faculty of Biomedical Sciences, Università della Svizzera italiana, Lugano, Switzerland.

9. Division of Nephrology, Ente Ospedaliero Cantonale, Lugano, Switzerland.

10. Clinical School, University of New South Wales, Sydney, New South Wales, Australia.

11. Clinical Trial Unit, Ente Ospedaliero Cantonale, Lugano, Switzerland.

12. Division of Clinical Pharmacology and Toxicology, Institute of Pharmacological Sciences of Southern Switzerland, Ente Ospedaliero Cantonale, Lugano, Switzerland.

13. Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, Zurich, Switzerland.

14. Department of Medicine, Ente Ospedaliero Cantonale, Bellinzona, Switzerland.

15. Institut Pasteur, Université Paris Cité, Lyssavirus Epidemiology and Neuropathology Unit, F-75015 Paris, France.

16. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.

17. Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA.

Abstract

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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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