title: Polyfunctional HIV-Specific Antibody Responses Are Associated with Spontaneous HIV Control.
abstract: Elite controllers (ECs) represent a unique model of a functional cure for HIV-1 infection as these individuals develop HIV-specific immunity able to persistently suppress viremia. Because accumulating evidence suggests that HIV controllers generate antibodies with enhanced capacity to drive antibody-dependent cellular cytotoxicity (ADCC) that may contribute to viral containment, we profiled an array of extra-neutralizing antibody effector functions across HIV-infected populations with varying degrees of viral control to define the characteristics of antibodies associated with spontaneous control. While neither the overall magnitude of antibody titer nor individual effector functions were increased in ECs, a more functionally coordinated innate immune-recruiting response was observed. Specifically, ECs demonstrated polyfunctional humoral immune responses able to coordinately recruit ADCC, other NK functions, monocyte and neutrophil phagocytosis, and complement. This functionally coordinated response was associated with qualitatively superior IgG3/IgG1 responses, whereas HIV-specific IgG2/IgG4 responses, prevalent among viremic subjects, were associated with poorer overall antibody activity. Rather than linking viral control to any single activity, this study highlights the critical nature of functionally coordinated antibodies in HIV control and associates this polyfunctionality with preferential induction of potent antibody subclasses, supporting coordinated antibody activity as a goal in strategies directed at an HIV-1 functional cure.
authors.affiliation: Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire, United States of America.
authors.forename: Margaret E
authors.initials: ME
authors.lastname: Ackerman
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts, United States of America.
authors.forename: Anastassia
authors.initials: A
authors.lastname: Mikhailova
authors.affiliation: Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire, United States of America.
authors.forename: Eric P
authors.initials: EP
authors.lastname: Brown
authors.affiliation: Department of Computer Science, Dartmouth College, Hanover, New Hampshire, United States of America.
authors.forename: Karen G
authors.initials: KG
authors.lastname: Dowell
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts, United States of America.|Howard Hughes Medical Institute, Chevy Chase, Maryland, United States of America.
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Walker
authors.affiliation: Department of Computer Science, Dartmouth College, Hanover, New Hampshire, United States of America.
authors.forename: Chris
authors.initials: C
authors.lastname: Bailey-Kellogg
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts, United States of America.
authors.forename: Todd J
authors.initials: TJ
authors.lastname: Suscovich
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts, United States of America.
authors.forename: Galit
authors.initials: G
authors.lastname: Alter
mesh_terms: D057134:Antibodies, Neutralizing / Q000276:immunology*; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology; D015483:HIV Antibodies / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D015483:HIV Antibodies; D007074:Immunoglobulin G