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

Hemagglutinin (HA) is the immunodominant protein of the influenza virus. We previously showed that mice injected with a monoglycosylated influenza A HA (HA mg ) produced cross-strain-reactive antibodies and were better protected than mice injected with a fully glycosylated HA (HA fg ) during lethal...

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Published inPLoS pathogens Vol. 17; no. 8; p. e1009724
Main Authors Ko, Yi-An, Yu, Yueh-Hsiang, Wu, Yen-Fei, Tseng, Yung-Chieh, Chen, Chia-Lin, Goh, King-Siang, Liao, Hsin-Yu, Chen, Ting-Hua, Cheng, Ting-Jen Rachel, Yang, An-Suei, Wong, Chi-Huey, Ma, Che, Lin, Kuo-I
Format Journal Article
LanguageEnglish
Published San Francisco, CA USA Public Library of Science 05.08.2021
Public Library of Science (PLoS)
Subjects
Analysis
Biology and life sciences
Care and treatment
Diagnosis
Influenza
Killer cells
Measurement
Medicine and Health Sciences
Monoclonal antibodies
Research and Analysis Methods
Risk factors
Taiwan
Online AccessGet full text

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Abstract Hemagglutinin (HA) is the immunodominant protein of the influenza virus. We previously showed that mice injected with a monoglycosylated influenza A HA (HA mg ) produced cross-strain-reactive antibodies and were better protected than mice injected with a fully glycosylated HA (HA fg ) 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 HA mg 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.
AbstractList Hemagglutinin (HA) is the immunodominant protein of the influenza virus. We previously showed that mice injected with a monoglycosylated influenza A HA (HA mg ) produced cross-strain-reactive antibodies and were better protected than mice injected with a fully glycosylated HA (HA fg ) 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 HA mg 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. 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.
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.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.
Hemagglutinin (HA) is the immunodominant protein of the influenza virus. We previously showed that mice injected with a monoglycosylated influenza A HA (HA.sub.mg) produced cross-strain-reactive antibodies and were better protected than mice injected with a fully glycosylated HA (HA.sub.fg) 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 HA.sub.mg 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.
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.
Hemagglutinin (HA) is the immunodominant protein of the influenza virus. We previously showed that mice injected with a monoglycosylated influenza A HA (HA mg ) produced cross-strain-reactive antibodies and were better protected than mice injected with a fully glycosylated HA (HA fg ) 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 HA mg 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.
Audience Academic
Author Ko, Yi-An
Goh, King-Siang
Chen, Ting-Hua
Cheng, Ting-Jen Rachel
Yang, An-Suei
Wu, Yen-Fei
Tseng, Yung-Chieh
Liao, Hsin-Yu
Ma, Che
Lin, Kuo-I
Wong, Chi-Huey
Yu, Yueh-Hsiang
Chen, Chia-Lin
AuthorAffiliation Genomics Research Center, Academia Sinica, Taipei, Taiwan
Johns Hopkins Bloomberg School of Public Health, UNITED STATES
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content type line 23
Current address: Merck Research Laboratory, Merck Sharp & Dohme (I.A.) LLC, Taiwan Branch, Taipei, Taiwan
Current address: Okinawa Institute of Science and Technology Graduate University, Onna, Okinawa, Japan
The authors have declared that no competing interests exist.
CM and K-IL share senior authorship on this work.
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Snippet Hemagglutinin (HA) is the immunodominant protein of the influenza virus. We previously showed that mice injected with a monoglycosylated influenza A HA (HA mg...
Hemagglutinin (HA) is the immunodominant protein of the influenza virus. We previously showed that mice injected with a monoglycosylated influenza A HA...
Hemagglutinin (HA) is the immunodominant protein of the influenza virus. We previously showed that mice injected with a monoglycosylated influenza A HA (HAmg)...
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SubjectTerms Analysis
Biology and life sciences
Care and treatment
Diagnosis
Influenza
Killer cells
Measurement
Medicine and Health Sciences
Monoclonal antibodies
Research and Analysis Methods
Risk factors
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Title A non-neutralizing antibody broadly protects against influenza virus infection by engaging effector cells
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https://pubmed.ncbi.nlm.nih.gov/PMC8341508
https://doaj.org/article/1d68c84373464a6bb70bde385675c643
Volume 17
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