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

Authors :
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
Source :
PLoS Pathogens, Vol 17, Iss 8 (2021)
Publication Year :
2021
Publisher :
Public Library of Science (PLoS), 2021.

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. Author summary The protective efficacy of antibodies is generally related to their neutralization potency. Here, we isolated a monoclonal antibody from mice injected with monoglycosylated hemagglutinin protein-based universal influenza vaccine, and demonstrated a head-domain recognizing, but non-neutralizing, monoclonal antibody carried prophylactic and therapeutic efficacy against a broad spectrum of influenza virus infections in vivo via effector functions.

Details

Language :
English
ISSN :
15537366 and 15537374
Volume :
17
Issue :
8
Database :
Directory of Open Access Journals
Journal :
PLoS Pathogens
Publication Type :
Academic Journal
Accession number :
edsdoj.74ae43827c054dd89beda4ed1ea0e547
Document Type :
article