Polyfunctional Hiv-Specific Antibody Responses Are Associated with Spontaneous Hiv Control

Authors

Margaret E. Ackerman, Dartmouth CollegeFollow
Anastassia Mikhailova, Ragon Institute of MGH, MIT, and Harvard
Eric P. Brown, Dartmouth College
Karen G. Dowell, Dartmouth College
Bruce D. Walker, Ragon Institute of MGH, MIT, and Harvard
Chris Bailey-Kellogg, Dartmouth CollegeFollow
Todd J. Suscovich, Ragon Institute of MGH, MIT, and Harvard
Galit Alter, Ragon Institute of MGH, MIT, and HarvardFollow

Document Type

Article

Publication Date

1-8-2016

Publication Title

PLoS Pathogens

Department

Thayer School of Engineering

Additional Department

Department of Computer Science

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.

DOI

10.1371/journal.ppat.1005315

Dartmouth Digital Commons Citation

Ackerman, Margaret E.; Mikhailova, Anastassia; Brown, Eric P.; Dowell, Karen G.; Walker, Bruce D.; Bailey-Kellogg, Chris; Suscovich, Todd J.; and Alter, Galit, "Polyfunctional Hiv-Specific Antibody Responses Are Associated with Spontaneous Hiv Control" (2016). Dartmouth Scholarship. 3044.
https://digitalcommons.dartmouth.edu/facoa/3044