<br><div> <head profile="http://www.w3.org/1999/xhtml/vocab"> <!--[if IE]><![endif]--> <meta http-equiv="Content-Type" content="text/html; charset=utf-8"/> <link rel="dns-prefetch" href="//scholar.google.com"/> <link rel="dns-prefetch" href="//pnas-movie.glencoesoftware.com"/> <link rel="dns-prefetch" href="//www.google.com"/> <link rel="dns-prefetch" href="//www.google-analytics.com"/> <link rel="dns-prefetch" href="//stats.g.doubleclick.net"/> <meta name="viewport" content="initial-scale=1, maximum-scale=1, width=device-width, user-scalable=yes"/> <link rel="shortcut icon" href="https://www.pnas.org/sites/default/files/images/favicon.ico" type="image/vnd.microsoft.icon"/> <link rel="canonical" href="https://www.pnas.org/content/early/2020/07/13/2008190117"/> <meta name="Generator" content="Drupal 7 (http://drupal.org)"/> <link rel="alternate" type="application/pdf" title="Full Text (PDF)" href="http://www.pnas.org/content/early/2020/07/13/2008190117.full.pdf"/> <link rel="alternate" type="text/plain" title="Full Text (Plain)" href="http://www.pnas.org/content/early/2020/07/13/2008190117.full.txt"/> <link rel="alternate" type="application/vnd.ms-powerpoint" title="Powerpoint" href="http://www.pnas.org/content/early/2020/07/13/2008190117.ppt"/> <meta name="citation_funding_source" content="citation_funder_id=100000002;citation_grant_number=RO1-AI145645;"/> <meta name="citation_funding_source" content="citation_funder_id=100000002;citation_grant_number=RO1-AI129802;"/> <meta name="citation_funding_source" content="citation_funder_id=100000002;citation_grant_number=RO1-AI129802;"/> <meta name="citation_funding_source" content="citation_funder_id=100000002;citation_grant_number=DP1-DA0333263;"/> <meta name="citation_funding_source" content="citation_funder_id=100000002;citation_grant_number=RO1-AI028433;"/> <meta name="citation_funding_source" content="citation_funder_id=100000002;citation_grant_number=RO1-OD011095;"/> <meta name="citation_funding_source" content="citation_funder_id=100000002;citation_grant_number=PO1-AI131365;"/> <meta name="citation_funding_source" content="citation_funder_id=100000865;citation_grant_number=OPP1169162;"/> <meta name="citation_funding_source" content="citation_funder_id=100000865;citation_grant_number=OPP1040731;"/> <meta name="citation_funding_source" content="citation_grant_number=89233218CNA000001;"/> <meta name="type" content="article"/> <meta name="category" content="research-article"/> <meta name="HW.identifier" content="/pnas/early/2020/07/13/2008190117.atom"/> <meta name="HW.pisa" content="pnas;2008190117v1"/> <meta name="DC.Format" content="text/html"/> <meta name="DC.Language" content="en"/> <meta name="DC.Title" content="Quantifying the contribution of Fc-mediated effector functions to the antiviral activity of anti–HIV-1 IgG1 antibodies in vivo"/> <meta name="DC.Identifier" content="10.1073/pnas.2008190117"/> <meta name="DC.Date" content="2020-07-14"/> <meta name="DC.Publisher" content="National Academy of Sciences"/> <meta name="DC.Rights" content="Copyright © 2020 the Author(s). Published by PNAS.. https://creativecommons.org/licenses/by-nc-nd/4.0/This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND)."/> <meta name="DC.AccessRights" content="open-access"/> <meta name="DC.Description" content="Virus-neutralizing monoclonal antibodies have been tested for the treatment or prevention of HIV-1 infection. Such an antibody can block virus infectivity and mediate killing of virus-infected cells by Fc-mediated effector functions. The relative contributions of these two antibody activities in vivo have not been quantified previously. By quantitatively analyzing results from experiments conducted in HIV-1–infected humanized mice and SHIV-infected rhesus macaques, we have determined that Fc-mediated effector functions contribute about 25–45% to the total antiviral activity of the anti–HIV-1 monoclonal antibodies tested. In combating viral infections, the Fab portion of an antibody could mediate virus neutralization, whereas Fc engagement of Fc-γ receptors (FcγRs) could mediate an array of effector functions. Evidence abounds that effector functions are important in controlling infections by influenza, Ebola, or HIV-1 in animal models. However, the relative contribution of virus neutralization versus effector functions to the overall antiviral activity of an antibody remains unknown. To address this fundamental question in immunology, we utilized our knowledge of HIV-1 dynamics to compare the kinetics of the viral load decline (ΔVL) in infected animals given a wild-type (WT) anti–HIV-1 immunoglobulin G1 (IgG1) versus those given a Fc-Null variant of the same antibody. In three independent experiments in HIV-1–infected humanized mice and one pivotal experiment in simian–human immunodeficiency virus (SHIV)-infected rhesus macaques, an earlier and sharper decline in viral load was consistently detected for the WT antibody. Quantifications of the observed differences indicate that Fc-mediated effector functions accounted for 25–45% of the total antiviral activity in these separate experiments. In this study, Fc-mediated effector functions have been quantified in vivo relative to the contribution of virus neutralization mediated by the Fab."/> <meta name="DC.Contributor" content="Pengfei Wang"/> <meta name="DC.Contributor" content="Mili R. Gajjar"/> <meta name="DC.Contributor" content="Jian Yu"/> <meta name="DC.Contributor" content="Neal N. Padte"/> <meta name="DC.Contributor" content="Agegnehu Gettie"/> <meta name="DC.Contributor" content="James L. Blanchard"/> <meta name="DC.Contributor" content="Kasi Russell-Lodrigue"/> <meta name="DC.Contributor" content="Laura E. Liao"/> <meta name="DC.Contributor" content="Alan S. Perelson"/> <meta name="DC.Contributor" content="Yaoxing Huang"/> <meta name="DC.Contributor" content="David D. Ho"/> <meta name="article:published_time" content="2020-07-14"/> <meta name="article:section" content="Biological Sciences"/> <meta name="citation_title" content="Quantifying the contribution of Fc-mediated effector functions to the antiviral activity of anti–HIV-1 IgG1 antibodies in vivo"/> <meta name="citation_abstract" lang="en" content="<p>In combating viral infections, the Fab portion of an antibody could mediate virus neutralization, whereas Fc engagement of Fc-γ receptors (FcγRs) could mediate an array of effector functions. Evidence abounds that effector functions are important in controlling infections by influenza, Ebola, or HIV-1 in animal models. However, the relative contribution of virus neutralization versus effector functions to the overall antiviral activity of an antibody remains unknown. To address this fundamental question in immunology, we utilized our knowledge of HIV-1 dynamics to compare the kinetics of the viral load decline (ΔVL) in infected animals given a wild-type (WT) anti–HIV-1 immunoglobulin G1 (IgG1) versus those given a Fc-Null variant of the same antibody. In three independent experiments in HIV-1–infected humanized mice and one pivotal experiment in simian–human immunodeficiency virus (SHIV)-infected rhesus macaques, an earlier and sharper decline in viral load was consistently detected for the WT antibody. Quantifications of the observed differences indicate that Fc-mediated effector functions accounted for 25–45% of the total antiviral activity in these separate experiments. In this study, Fc-mediated effector functions have been quantified in vivo relative to the contribution of virus neutralization mediated by the Fab.</p>"/> <meta name="citation_abstract" lang="en" scheme="executive-summary" content="<h3>Significance</h3> <p>Virus-neutralizing monoclonal antibodies have been tested for the treatment or prevention of HIV-1 infection. Such an antibody can block virus infectivity and mediate killing of virus-infected cells by Fc-mediated effector functions. The relative contributions of these two antibody activities in vivo have not been quantified previously. By quantitatively analyzing results from experiments conducted in HIV-1–infected humanized mice and SHIV-infected rhesus macaques, we have determined that Fc-mediated effector functions contribute about 25–45% to the total antiviral activity of the anti–HIV-1 monoclonal antibodies tested.</p>"/> <meta name="citation_journal_title" content="Proceedings of the National Academy of Sciences"/> <meta name="citation_publisher" content="National Academy of Sciences"/> <meta name="citation_publication_date" content="2020/07/14"/> <meta name="citation_mjid" content="pnas;2008190117v1"/> <meta name="citation_id" content="2008190117v1"/> <meta name="citation_public_url" content="https://www.pnas.org/content/early/2020/07/13/2008190117"/> <meta name="citation_abstract_html_url" content="https://www.pnas.org/content/early/2020/07/13/2008190117.abstract"/> <meta name="citation_full_html_url" content="https://www.pnas.org/content/early/2020/07/13/2008190117.full"/> <meta name="citation_pdf_url" content="https://www.pnas.org/content/pnas/early/2020/07/13/2008190117.full.pdf"/> <meta name="citation_issn" content="0027-8424"/> <meta name="citation_issn" content="1091-6490"/> <meta name="citation_journal_abbrev" content="PNAS"/> <meta name="citation_doi" content="10.1073/pnas.2008190117"/> <meta name="citation_pmid" content="32665438"/> <meta name="citation_num_pages" content="8"/> <meta name="citation_article_type" content="Research Article"/> <meta name="citation_section" content="Biological Sciences"/> <meta name="citation_access" content="all"/> <meta name="citation_author" content="Pengfei Wang"/> <meta name="citation_author_institution" content="Columbia University Vagelos College of Physicians and Surgeons"/> <meta name="citation_author_orcid" content="https://orcid.org/0000-0003-2454-7652"/> <meta name="citation_author" content="Mili R. 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Virol.;citation_author=M. S. Seaman;citation_title=Tiered categorization of a diverse panel of HIV-1 Env pseudoviruses for assessment of neutralizing antibodies;citation_volume=84;citation_year=2010;citation_pmid=19939925;citation_doi=10.1128/JVI.02108-09"/> <meta name="citation_fulltext_world_readable" content=""/> <meta name="twitter:title" content="Quantifying the contribution of Fc-mediated effector functions to the antiviral activity of anti–HIV-1 IgG1 antibodies in vivo"/> <meta name="twitter:card" content="summary_large_image"/> <meta name="twitter:image" content="https://www.pnas.org/content/early/2020/07/13/2008190117/F1.large.jpg"/> <meta name="twitter:description" content="Virus-neutralizing monoclonal antibodies have been tested for the treatment or prevention of HIV-1 infection. Such an antibody can block virus infectivity and mediate killing of virus-infected cells by Fc-mediated effector functions. The relative contributions of these two antibody activities in vivo have not been quantified previously. By quantitatively analyzing results from experiments conducted in HIV-1–infected humanized mice and SHIV-infected rhesus macaques, we have determined that Fc-mediated effector functions contribute about 25–45% to the total antiviral activity of the anti–HIV-1 monoclonal antibodies tested. In combating viral infections, the Fab portion of an antibody could mediate virus neutralization, whereas Fc engagement of Fc-γ receptors (FcγRs) could mediate an array of effector functions. Evidence abounds that effector functions are important in controlling infections by influenza, Ebola, or HIV-1 in animal models. However, the relative contribution of virus neutralization versus effector functions to the overall antiviral activity of an antibody remains unknown. To address this fundamental question in immunology, we utilized our knowledge of HIV-1 dynamics to compare the kinetics of the viral load decline (ΔVL) in infected animals given a wild-type (WT) anti–HIV-1 immunoglobulin G1 (IgG1) versus those given a Fc-Null variant of the same antibody. In three independent experiments in HIV-1–infected humanized mice and one pivotal experiment in simian–human immunodeficiency virus (SHIV)-infected rhesus macaques, an earlier and sharper decline in viral load was consistently detected for the WT antibody. Quantifications of the observed differences indicate that Fc-mediated effector functions accounted for 25–45% of the total antiviral activity in these separate experiments. In this study, Fc-mediated effector functions have been quantified in vivo relative to the contribution of virus neutralization mediated by the Fab."/> <meta name="og-title" property="og:title" content="Quantifying the contribution of Fc-mediated effector functions to the antiviral activity of anti–HIV-1 IgG1 antibodies in vivo"/> <meta name="og-url" property="og:url" content="https://www.pnas.org/content/early/2020/07/13/2008190117"/> <meta name="og-site-name" property="og:site_name" content="PNAS"/> <meta name="og-description" property="og:description" content="Virus-neutralizing monoclonal antibodies have been tested for the treatment or prevention of HIV-1 infection. Such an antibody can block virus infectivity and mediate killing of virus-infected cells by Fc-mediated effector functions. The relative contributions of these two antibody activities in vivo have not been quantified previously. By quantitatively analyzing results from experiments conducted in HIV-1–infected humanized mice and SHIV-infected rhesus macaques, we have determined that Fc-mediated effector functions contribute about 25–45% to the total antiviral activity of the anti–HIV-1 monoclonal antibodies tested. In combating viral infections, the Fab portion of an antibody could mediate virus neutralization, whereas Fc engagement of Fc-γ receptors (FcγRs) could mediate an array of effector functions. Evidence abounds that effector functions are important in controlling infections by influenza, Ebola, or HIV-1 in animal models. However, the relative contribution of virus neutralization versus effector functions to the overall antiviral activity of an antibody remains unknown. To address this fundamental question in immunology, we utilized our knowledge of HIV-1 dynamics to compare the kinetics of the viral load decline (ΔVL) in infected animals given a wild-type (WT) anti–HIV-1 immunoglobulin G1 (IgG1) versus those given a Fc-Null variant of the same antibody. In three independent experiments in HIV-1–infected humanized mice and one pivotal experiment in simian–human immunodeficiency virus (SHIV)-infected rhesus macaques, an earlier and sharper decline in viral load was consistently detected for the WT antibody. Quantifications of the observed differences indicate that Fc-mediated effector functions accounted for 25–45% of the total antiviral activity in these separate experiments. In this study, Fc-mediated effector functions have been quantified in vivo relative to the contribution of virus neutralization mediated by the Fab."/> <meta name="og-type" property="og:type" content="article"/> <meta name="og-image" property="og:image" content="https://www.pnas.org/content/early/2020/07/13/2008190117/F1.large.jpg"/> <meta name="format-detection" content="telephone=no"/> <title>Quantifying the contribution of Fc-mediated effector functions to the antiviral activity of anti–HIV-1 IgG1 antibodies in vivo | PNAS</title> <link type="text/css" rel="stylesheet" href="https://www.pnas.org/sites/default/files/advagg_css/css__zUOsaJT2-txr78Pro2jqp5HkKYs7CY9FbkfBemQXYlw__kiQOVz2drquY4Y9F8gINaFiOXWD3R3YCpizYXeeITSI__Jsi9FELnOGd8Izl-cQZlaPD8YovR4Sb_o7kms4MEc0E.css" media="all"/> <link type="text/css" rel="stylesheet" href="https://www.pnas.org/sites/all/modules/highwire/highwire/highwire.style.highwire.css?qdilw1" media="all"/> <link type="text/css" rel="stylesheet" href="https://www.pnas.org/sites/default/files/advagg_css/css__IBZ9mHpn46TRp2BimuZ9LV8gzg5ve38Vt8Ur3OYiiIE__NtZxs4y1UkEH1BmzA2899OuPWrL4Vyfw35jNwF7gpGQ__Jsi9FELnOGd8Izl-cQZlaPD8YovR4Sb_o7kms4MEc0E.css" media="all"/> <link type="text/css" rel="stylesheet" href="//cdn.jsdelivr.net/qtip2/2.2.1/jquery.qtip.min.css" media="all"/> <link type="text/css" rel="stylesheet" href="https://www.pnas.org/sites/default/files/advagg_css/css__22ZTiNg-l1Oh3N_2YNTtQtEIQm3aRzbkzzzbjY2p8xQ__X6SoMpUVch0hUZhU5GhhA43N8gkW5jGOyL-zhqU413o__Jsi9FELnOGd8Izl-cQZlaPD8YovR4Sb_o7kms4MEc0E.css" media="all"/> <link type="text/css" rel="stylesheet" href="//pnas-movie.glencoesoftware.com/static/video-js.min.css" media="all"/> <link type="text/css" rel="stylesheet" href="https://www.pnas.org/sites/default/files/advagg_css/css__7CYEtfDxMu3CEBZ53TQrEfMpO7duR_XdIuTLye9W7Cc__CzzPXev2zJRWVry4kyDAKuuERTizWaGzrN8gCp2auaE__Jsi9FELnOGd8Izl-cQZlaPD8YovR4Sb_o7kms4MEc0E.css" media="all"/> <link type="text/css" rel="stylesheet" href="https://www.pnas.org/sites/default/files/advagg_css/css__SFa0RaACUzIjJkHcYBtVK313lbEjuTFPdV1LDKDJEjo__jXPoluCdY9OJ1bes_FwCXcdI2BYpoO-G9OnF0StiEQA__Jsi9FELnOGd8Izl-cQZlaPD8YovR4Sb_o7kms4MEc0E.css" media="all"/> <!--[if lt IE 9]><![endif]--> <!--[if lt IE 10]><![endif]--> </head> <body id="wp_automatic_ReadabilityBody"> <!-- Google Tag Manager --> <noscript><iframe src="http://www.googletagmanager.com/ns.html?id=GTM-NDVQMQ4" height="0" width="0" style="display:none;visibility:hidden"></iframe></noscript> <!-- End Google Tag Manager --> <div class="page" id="page"> <!-- /.section-header --> <section role="main" class="section section-content" id="section-content"> <div class="container-fluid zone-wrapper zone-content-wrapper"> <div class="zone zone-content row"> <div class="region region-content col-narrow-22 col-narrow-offset-1"> <div id="block-panels-mini-whats-new-in" class="block block-panels-mini"> <div class="content"> <div class="panel-display panel-1col clearfix" id="mini-panel-whats_new_in"> <div class="panel-panel panel-col"> <div> <div class="panel-pane pane-snippet pane-pnas-physical-sciences wni-dropdown"> <h3 class="pane-title"><span class="pane-title-text">Physical Sciences</span></h3> <div class="pane-content"> <div class="pnas-physical-sciences" id="pnas-physical-sciences"> <div class="snippet-content"> <h4>Featured Portals</h4> <h4>Articles by Topic</h4> </div> </div> </div> </div> <div class="panel-pane pane-snippet pane-pnas-social-sciences wni-dropdown"> <h3 class="pane-title"><span class="pane-title-text">Social Sciences</span></h3> <div class="pane-content"> <div class="pnas-social-sciences" id="pnas-social-sciences"> <div class="snippet-content"> <h4>Featured Portals</h4> <h4>Articles by Topic</h4> </div> </div> </div> </div> <div class="panel-pane pane-snippet pane-pnas-biological-sciences wni-dropdown"> <h3 class="pane-title"><span class="pane-title-text">Biological Sciences</span></h3> <div class="pane-content"> <div class="pnas-biological-sciences" id="pnas-biological-sciences"> <div class="snippet-content"> <h4>Featured Portals</h4> <h4>Articles by Topic</h4> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div><!-- /.zone-content --> </div><!-- /.zone-content-wrapper --> </section> <!-- /.section-content --> <!-- /.section-footer --> </div> <!-- /.page --> </body> </div>