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
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibodies, Monoclonal / immunology
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Antibodies, Monoclonal / pharmacology*
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Antibodies, Neutralizing / immunology
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Antibodies, Neutralizing / pharmacology*
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Antibodies, Viral / immunology
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Antibodies, Viral / pharmacology
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Antibody-Dependent Cell Cytotoxicity*
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Female
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Hemagglutinin Glycoproteins, Influenza Virus / immunology
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Influenza A virus / immunology*
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Killer Cells, Natural / drug effects
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Killer Cells, Natural / immunology*
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Killer Cells, Natural / virology
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Macrophages, Alveolar / drug effects
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Macrophages, Alveolar / immunology*
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Macrophages, Alveolar / virology
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Mice
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Mice, Inbred BALB C
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Orthomyxoviridae Infections / immunology
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Orthomyxoviridae Infections / prevention & control*
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Orthomyxoviridae Infections / virology
Substances
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Antibodies, Monoclonal
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Antibodies, Neutralizing
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Antibodies, Viral
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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.