A non-neutralizing antibody broadly protects against influenza virus infection by engaging effector cells

Yi-An Ko; Yueh-Hsiang Yu; Yen-Fei Wu; Yung-Chieh Tseng; Chia-Lin Chen; King-Siang Goh; Hsin-Yu Liao; Ting-Hua Chen; Ting-Jen Rachel Cheng; An-Suei Yang; Chi-Huey Wong; Che Ma; Kuo-I Lin

doi:10.1371/journal.ppat.1009724

A non-neutralizing antibody broadly protects against influenza virus infection by engaging effector cells

PLoS Pathog. 2021 Aug 5;17(8):e1009724. doi: 10.1371/journal.ppat.1009724. eCollection 2021 Aug.

Authors

Affiliation

¹ Genomics Research Center, Academia Sinica, Taipei, Taiwan.

Abstract

Hemagglutinin (HA) is the immunodominant protein of the influenza virus. We previously showed that mice injected with a monoglycosylated influenza A HA (HAmg) produced cross-strain-reactive antibodies and were better protected than mice injected with a fully glycosylated HA (HAfg) during lethal dose challenge. We employed a single B-cell screening platform to isolate the cross-protective monoclonal antibody (mAb) 651 from mice immunized with the HAmg of A/Brisbane/59/2007 (H1N1) influenza virus (Bris/07). The mAb 651 recognized the head domain of a broad spectrum of HAs from groups 1 and 2 influenza A viruses and offered prophylactic and therapeutic efficacy against A/California/07/2009 (H1N1) (Cal/09) and Bris/07 infections in mice. The antibody did not possess neutralizing activity; however, antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis mediated by natural killer cells and alveolar macrophages were important in the protective efficacy of mAb 651. Together, this study highlighted the significance of effector functions for non-neutralizing antibodies to exhibit protection against influenza virus infection.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antibodies, Monoclonal / immunology
Antibodies, Monoclonal / pharmacology*
Antibodies, Neutralizing / immunology
Antibodies, Neutralizing / pharmacology*
Antibodies, Viral / immunology
Antibodies, Viral / pharmacology
Antibody-Dependent Cell Cytotoxicity*
Female
Hemagglutinin Glycoproteins, Influenza Virus / immunology
Influenza A virus / immunology*
Killer Cells, Natural / drug effects
Killer Cells, Natural / immunology*
Killer Cells, Natural / virology
Macrophages, Alveolar / drug effects
Macrophages, Alveolar / immunology*
Macrophages, Alveolar / virology
Mice
Mice, Inbred BALB C
Orthomyxoviridae Infections / immunology
Orthomyxoviridae Infections / prevention & control*
Orthomyxoviridae Infections / virology

Substances

Antibodies, Monoclonal
Antibodies, Neutralizing
Antibodies, Viral
Hemagglutinin Glycoproteins, Influenza Virus

Grants and funding

This work was supported by grants from Academia Sinica (AS-SUMMIT-109 to CHW, AS-IA-107-L05 to KIL; https://www.sinica.edu.tw/en), Taiwan, and Ministry of Science and Technology (MOST 109-2320-B-001-023-MY3 to KIL; https://www.most.gov.tw/?l=en). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.