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

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

doi:10.1371/journal.ppat.1009724

Yi-An Ko, Yen-Fei Wu + Show 12 more

Open Access

https://doi.org/10.1371/journal.ppat.1009724

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Journal: PLoS Pathogens	Publication Date: Aug 5, 2021
Citations: 15	License type: CC BY 4.0

Affiliation: Genomics Research Center, Academia Sinica

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.

Highlights

Influenza viral infections cause a contagious respiratory illness of the upper airways and lungs
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
Protective antibody against influenza neutralizing monoclonal antibody (mAb) from mice immunized with HAmg proteins prepared from the A/Brisbane/ 59/2007 (H1N1) (Bris/07) influenza virus

Summary

Introduction

Influenza viral infections cause a contagious respiratory illness of the upper airways and lungs. Half a million deaths worldwide are due to seasonal influenza each year [1]. Influenza viruses are classified into four subtypes: A, B, C, and D. The A and B subtypes are responsible for the seasonal influenza in humans [2]. More severe complications resulting from influenza viral infection and a loss of influenza vaccine efficacy have been found in older adults [4,5]. There remains a need to develop new strategies to overcome the moderate responses and narrow coverage range of the current flu vaccine

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