Protective human antibodies against a conserved epitope in pre- and postfusion influenza hemagglutinin-Reference-Cited by-同舟云学术

Protective human antibodies against a conserved epitope in pre- and postfusion influenza hemagglutinin

Published:2023-12-26 Issue:1 Volume:121 Page:
ISSN:0027-8424
Container-title:Proceedings of the National Academy of Sciences
language:en
Short-container-title:Proc. Natl. Acad. Sci. U.S.A.

Author:

Finney Joel¹²,Moseman Annie Park²,Kong Susan¹,Watanabe Akiko²,Song Shengli³,Walsh Richard M.⁴⁵,Kuraoka Masayuki²,Kotaki Ryutaro²,Moseman E. Ashley²,McCarthy Kevin R.⁶^ORCID,Liao Dongmei²,Liang Xiaoe²,Nie Xiaoyan²,Lavidor Olivia¹,Abbott Richard¹,Harrison Stephen C.¹⁷^ORCID,Kelsoe Garnett²³⁸^ORCID

Affiliation:

1. Laboratory of Molecular Medicine, Children’s Hospital, Harvard Medical School, Boston, MA 02115

2. Department of Integrative Immunobiology, Duke University, Durham, NC 27710

3. Department of Surgery, Duke University, Durham, NC 27710

4. The Harvard Cryo-Electron Microscopy (Cryo-EM) Center for Structural Biology, Harvard Medical School, Boston, MA 02115

5. Department of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115

6. Center for Vaccine Research, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261

7. HHMI, Boston, MA 02115

8. Duke Human Vaccine Institute, Duke University, Durham, NC 27710

Abstract

Phylogenetically and antigenically distinct influenza A and B viruses (IAV and IBV) circulate in human populations, causing widespread morbidity. Antibodies (Abs) that bind epitopes conserved in both IAV and IBV hemagglutinins (HAs) could protect against disease by diverse virus subtypes. Only one reported HA Ab, isolated from a combinatorial display library, protects against both IAV and IBV. Thus, there has been so far no information on the likelihood of finding naturally occurring human Abs that bind HAs of diverse IAV subtypes and IBV lineages. We have now recovered from several unrelated human donors five clonal Abs that bind a conserved epitope preferentially exposed in the postfusion conformation of IAV and IVB HA2. These Abs lack neutralizing activity in vitro but in mice provide strong, IgG subtype–dependent protection against lethal IAV and IBV infections. Strategies to elicit similar Abs routinely might contribute to more effective influenza vaccines.

Funder

HHS | NIH | National Institute of Allergy and Infectious Diseases

Howard Hughes Medical Institute

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

Link

https://pnas.org/doi/pdf/10.1073/pnas.2316964120

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1. Protective human antibodies against a conserved epitope in pre- and postfusion influenza hemagglutinin;Proceedings of the National Academy of Sciences;2023-12-26