Tracking the Trajectory of Functional Humoral Immune Responses Following Acute HIV Infection.

Autor:	Jennewein MF; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, United States., Mabuka J; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, United States.; Africa Health Research Institute, Durban, South Africa.; HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa., Papia CL; Thayer School of Engineering, Dartmouth College, Hanover, NH, United States., Boudreau CM; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, United States., Dong KL; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, United States., Ackerman ME; Thayer School of Engineering, Dartmouth College, Hanover, NH, United States., Ndung'u T; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, United States.; Africa Health Research Institute, Durban, South Africa.; HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa.; Max Planck Institute for Infection Biology, Berlin, Germany.; Division of Infection and Immunity, University College London, London, United Kingdom., Alter G; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2020 Aug 07; Vol. 11, pp. 1744. Date of Electronic Publication: 2020 Aug 07 (Print Publication: 2020).
DOI:	10.3389/fimmu.2020.01744
Abstrakt:	Increasing evidence points to a role for antibody-mediated effector functions in preventing and controlling HIV infection. However, less is known about how these antibody effector functions evolve following infection. Moreover, how the humoral immune response is naturally tuned to recruit the antiviral activity of the innate immune system, and the extent to which these functions aid in the control of infection, are poorly understood. Using plasma samples from 10 hyper-acute HIV-infected South African women, identified in Fiebig stage I (the FRESH cohort), systems serology was performed to evaluate the functional and biophysical properties of gp120-, gp41-, and p24- specific antibody responses during the first year of infection. Significant changes were observed in both the functional and biophysical characteristics of the humoral immune response following acute HIV infection. Antibody Fc-functionality increased over the course of infection, with increases in antibody-mediated phagocytosis, NK activation, and complement deposition occurring in an antigen-specific manner. Changes in both antibody subclass and antibody Fc-glycosylation drove the evolution of antibody effector activity, highlighting natural modifications in the humoral immune response that may enable the directed recruitment of the innate immune system to target and control HIV. Moreover, enhanced antibody functionality, particularly gp120-specific polyfunctionality, was tied to improvements in clinical course of infection, supporting a role for functional antibodies in viral control. (Copyright © 2020 Jennewein, Mabuka, Papia, Boudreau, Dong, Ackerman, Ndung'u and Alter.)
Databáze:	MEDLINE
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