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  1. Article ; Online: Hemagglutinin stalk-binding antibodies enhance effectiveness of neuraminidase inhibitors against influenza via Fc-dependent effector functions.

    Zhang, Ali / Chaudhari, Hanu / Agung, Yonathan / D'Agostino, Michael R / Ang, Jann C / Tugg, Yona / Miller, Matthew S

    Cell reports. Medicine

    2022  Volume 3, Issue 8, Page(s) 100718

    Abstract: The conserved hemagglutinin stalk domain is an attractive target for broadly effective antibody-based therapeutics and next-generation universal influenza vaccines. Protection provided by hemagglutinin stalk-binding antibodies is principally mediated ... ...

    Abstract The conserved hemagglutinin stalk domain is an attractive target for broadly effective antibody-based therapeutics and next-generation universal influenza vaccines. Protection provided by hemagglutinin stalk-binding antibodies is principally mediated through activation of immune effector cells. Titers of stalk-binding antibodies are highly variable on an individual level and tend to increase with age as a result of increasing exposures to influenza virus. In our study, we show that stalk-binding antibodies cooperate with neuraminidase inhibitors to protect against influenza virus infection in an Fc-dependent manner. These data suggest that the effectiveness of neuraminidase inhibitors is likely influenced by an individual's titers of stalk-binding antibodies and that neuraminidase inhibitors may enhance the effectiveness of future stalk-binding monoclonal antibody-based treatments.
    MeSH term(s) Antibodies, Viral ; Hemagglutinin Glycoproteins, Influenza Virus/chemistry ; Hemagglutinins ; Humans ; Immunoglobulin Fc Fragments/immunology ; Influenza Vaccines ; Influenza, Human/drug therapy ; Neuraminidase ; Orthomyxoviridae
    Chemical Substances Antibodies, Viral ; Hemagglutinin Glycoproteins, Influenza Virus ; Hemagglutinins ; Immunoglobulin Fc Fragments ; Influenza Vaccines ; Neuraminidase (EC 3.2.1.18)
    Language English
    Publishing date 2022-08-10
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2666-3791
    ISSN (online) 2666-3791
    DOI 10.1016/j.xcrm.2022.100718
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Beyond neutralization: Fc-dependent antibody effector functions in SARS-CoV-2 infection.

    Zhang, Ali / Stacey, Hannah D / D'Agostino, Michael R / Tugg, Yona / Marzok, Art / Miller, Matthew S

    Nature reviews. Immunology

    2022  Volume 23, Issue 6, Page(s) 381–396

    Abstract: Neutralizing antibodies are known to have a crucial role in protecting against SARS-CoV-2 infection and have been suggested to be a useful correlate of protection for vaccine clinical trials and for population-level surveys. In addition to neutralizing ... ...

    Abstract Neutralizing antibodies are known to have a crucial role in protecting against SARS-CoV-2 infection and have been suggested to be a useful correlate of protection for vaccine clinical trials and for population-level surveys. In addition to neutralizing virus directly, antibodies can also engage immune effectors through their Fc domains, including Fc receptor-expressing immune cells and complement. The outcome of these interactions depends on a range of factors, including antibody isotype-Fc receptor combinations, Fc receptor-bearing cell types and antibody post-translational modifications. A growing body of evidence has shown roles for these Fc-dependent antibody effector functions in determining the outcome of SARS-CoV-2 infection. However, measuring these functions is more complicated than assays that measure antibody binding and virus neutralization. Here, we examine recent data illuminating the roles of Fc-dependent antibody effector functions in the context of SARS-CoV-2 infection, and we discuss the implications of these data for the development of next-generation SARS-CoV-2 vaccines and therapeutics.
    MeSH term(s) Humans ; COVID-19 ; COVID-19 Vaccines ; Antibodies, Viral ; SARS-CoV-2 ; Antibodies, Neutralizing ; Immunoglobulin Fc Fragments ; Receptors, Fc
    Chemical Substances COVID-19 Vaccines ; Antibodies, Viral ; Antibodies, Neutralizing ; Immunoglobulin Fc Fragments ; Receptors, Fc
    Language English
    Publishing date 2022-12-19
    Publishing country England
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 2062776-2
    ISSN 1474-1741 ; 1474-1733
    ISSN (online) 1474-1741
    ISSN 1474-1733
    DOI 10.1038/s41577-022-00813-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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