Temporal variation in HIV-specific IgG subclass Abs during acute infection differentiates spontaneous controllers from chronic progressors
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Author(s)
Sadanand, Saheli
Schoen, Matthew K.
Lane, Sophie
Streeck, Hendrik
Smith, Davey
Little, Susan
Richman, Douglas
Das, Jishnu
Chung, Amy H
Suscovich, Todd J
Date Issued
December 2017
Journal
AIDS
Publisher
Ovid Technologies (Wolters Kluwer Health)
Citation
Sadanand, Saheli, Jishnu Das, Amy W. Chung, Matthew K. Schoen, Sophie Lane, Todd J. Suscovich, Hendrik Streeck, et al. “Temporal Variation in HIV-Specific IgG Subclass Abs During Acute Infection Differentiates Spontaneous Controllers from Chronic Progressors.” AIDS (December 2017): 1.
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Author's final manuscript
Abstract
Objective: Given the emerging appreciation for the role of antibody-dependent effector functions and IgG subclass distribution among spontaneous controllers of HIV, we sought to determine whether antibody-Associated features diverged in early HIV infection between patients who ultimately became controllers versus those who became progressors. Methods: IgG was purified from plasma from nine acutely infected patients who subsequently controlled HIV spontaneously (controllers) and 10 acutely infected individuals who did not control viremia (progressors). Antibody profiles were compared at weeks 4, 12, 24 and 48 postinfection. Levels of clade B gp120-specific, gp140-specific and gp41-specific IgG antibody subclasses were measured. In addition, gp120-specific antibody-dependent cellular phagocytosis, rapid fluorescent antibody-dependent cellular cytotoxicity and antibody-dependent cellular viral inhibition were all assessed. Results: Although no single antibody-related measurement was significantly associated with long-Term HIV control, combinations of antibody-Associated variables were able to accurately differentiate controllers and progressors. In contrast to controllers, progressors showed greater dynamic changes in gp120-specific subclass selection profiles, with increasing levels of Env-specific IgG2 antibodies and losses in Env-specific IgG3 antibodies. Moreover, progressors, but not controllers, lost antibody-dependent cellular viral inhibition function over time. Together, these results highlight changes in IgG subclass selection profiles in progressive, but not controlled, HIV infection. Conclusion: This study suggests that the temporal variation and maintenance of Env-specific IgG subclasses during acute HIV infection are predictive of eventual disease control. The maintenance of gp120-specific and gp140-specific IgG3 may contribute to control of disease in spontaneous controllers. Thus, strategies to induce stable IgG3 responses may preserve control of the viral reservoir.
MIT Department
Massachusetts Institute of Technology. Anthropology Program
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Chemical Engineering
Massachusetts Institute of Technology. Department of Civil and Environmental Engineering
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DOI of Published Version
https://doi.org/10.1097/QAD.0000000000001716
