Tracking the Trajectory of Functional Humoral Immune Responses Following Acute HIV Infection
Open Access
- 7 August 2020
- journal article
- research article
- Published by Frontiers Media SA in Frontiers in Immunology
- Vol. 11, 1744
- https://doi.org/10.3389/fimmu.2020.01744
Abstract
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.This publication has 85 references indexed in Scilit:
- Immune-Correlates Analysis of an HIV-1 Vaccine Efficacy TrialThe New England Journal of Medicine, 2012
- Initial antibodies binding to HIV-1 gp41 in acutely infected subjects are polyreactive and highly mutatedThe Journal of Experimental Medicine, 2011
- Decreased Fc receptor expression on innate immune cells is associated with impaired antibody-mediated cellular phagocytic activity in chronically HIV-1 infected individualsVirology, 2011
- A robust, high-throughput assay to determine the phagocytic activity of clinical antibody samplesJournal of Immunological Methods, 2011
- Antibodies mediate intracellular immunity through tripartite motif-containing 21 (TRIM21)Proceedings of the National Academy of Sciences of the United States of America, 2010
- The Humoral Response to HIV‐1: New Insights, Renewed FocusThe Journal of Infectious Diseases, 2010
- Role of Humoral Immunity in Host Defense Against HIVCurrent HIV/AIDS Reports, 2010
- The immune response during acute HIV-1 infection: clues for vaccine developmentNature Reviews Immunology, 2009
- HIV-1-specific antibody responses during acute and chronic HIV-1 infectionCurrent Opinion in HIV and AIDS, 2009
- HIV infection and the gastrointestinal immune systemMucosal Immunology, 2007