title: Fc receptor-mediated phagocytosis in tissues as a potent mechanism for preventive and therapeutic HIV vaccine strategies.
abstract: Although the development of a fully protective HIV vaccine is the ultimate goal of HIV research, to date only one HIV vaccine trial, the RV144, has successfully induced a weakly protective response. The 31% protection from infection achieved in the RV144 trial was linked to the induction of nonneutralizing antibodies, able to mediate antibody-dependent cell-mediated cytotoxicity (ADCC), suggestive of an important role of Fc-mediated functions in protection. Similarly, Fc-mediated antiviral activity was recently shown to play a critical role in actively suppressing the viral reservoir, but the Fc effector mechanisms within tissues that provide protection from or after infection are largely unknown. Here we aimed to define the landscape of effector cells and Fc receptors present within vulnerable tissues. We found negligible Fc receptor-expressing natural killer cells in the female reproductive and gastrointestinal mucosa. Conversely, Fc receptor-expressing macrophages were highly enriched in most tissues, but neutrophils mediated superior antibody-mediated phagocytosis. Modifications in Fc domain of VRC01 antibody increased phagocytic responses in both phagocytes. These data suggest that non-ADCC-mediated mechanisms, such as phagocytosis and neutrophil activation, are more likely to play a role in preventative vaccine or reservoir-eliminating therapeutic approaches.
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts, USA.|Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: Sips
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts, USA.
authors.forename: M
authors.initials: M
authors.lastname: Krykbaeva
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts, USA.
authors.forename: T J
authors.initials: TJ
authors.lastname: Diefenbach
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts, USA.
authors.forename: M
authors.initials: M
authors.lastname: Ghebremichael
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts, USA.
authors.forename: B A
authors.initials: BA
authors.lastname: Bowman
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts, USA.
authors.forename: A-S
authors.initials: AS
authors.lastname: Dugast
authors.affiliation: Thayer School of Engineering at Dartmouth College, Hanover, New Hampshire, USA.
authors.forename: A W
authors.initials: AW
authors.lastname: Boesch
authors.affiliation: Institute of HIV Research, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Streeck
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts, USA.
authors.forename: D S
authors.initials: DS
authors.lastname: Kwon
authors.affiliation: Thayer School of Engineering at Dartmouth College, Hanover, New Hampshire, USA.
authors.forename: M E
authors.initials: ME
authors.lastname: Ackerman
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts, USA.
authors.forename: T J
authors.initials: TJ
authors.lastname: Suscovich
authors.affiliation: Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
authors.forename: P
authors.initials: P
authors.lastname: Brouckaert
authors.affiliation: Division of Infectious Diseases, University of Minnesota, Minneapolis, Minnesota, USA.
authors.forename: T W
authors.initials: TW
authors.lastname: Schacker
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts, USA.
authors.forename: G
authors.initials: G
authors.lastname: Alter
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology; D015415:Biomarkers; D000080908:Broadly Neutralizing Antibodies; D016207:Cytokines / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D015483:HIV Antibodies / Q000276:immunology; D015658:HIV Infections / Q000276:immunology* / Q000378:metabolism* / Q000517:prevention & control / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D018836:Inflammation Mediators / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008875:Middle Aged; D009092:Mucous Membrane / Q000276:immunology / Q000378:metabolism / Q000821:virology; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D010587:Phagocytosis / Q000276:immunology*; D011961:Receptors, Fc / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
chemical_list: D016915:AIDS Vaccines; D000911:Antibodies, Monoclonal; D015415:Biomarkers; D000080908:Broadly Neutralizing Antibodies; D016207:Cytokines; D015483:HIV Antibodies; D018836:Inflammation Mediators; D011961:Receptors, Fc; C578595:VRC01 monoclonal antibody