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AIDS Res Hum Retroviruses. 2019 Aug 21. doi: 10.1089/AID.2019.0047. [Epub ahead of print]

Boosting of Markers of Fcγ Receptor Function in Anti-HIV Antibodies During Structured Treatment Interruption.

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Immune Therapies Group, Life Sciences, Burnet Institute, Melbourne, Australia.
Department of Immunology, Monash University Central Clinical School, Melbourne, Australia.
Department of Pathology, The University of Melbourne, Melbourne, Australia.
Australian Red Cross Blood Service, Alexandria, Australia.
School of Medical Science, Faculty of Medicine and Health, University of Sydney, Sydney, Australia.
Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Australia.
Disease Elimination, Life Sciences, Burnet Institute, Melbourne, Australia.
Department of Infectious Diseases, Melbourne Sexual Health Centre, Alfred Health, Central Clinical School, Monash University, Melbourne, Australia.


Anti-HIV envelope (Env) antibodies elicit important Fc receptor functions, including FcγRIIIa-mediated natural killer cell killing of opsonized infected targets. How these antibodies evolve during HIV infection and treatment remains poorly understood. We describe changes in anti-HIV Env IgG using longitudinal samples from seroconverter subjects treated soon after infection and later during periods of structured treatment interruption (STI). Our well-validated dimeric rsFcγR binding assays combine effects of opsonizing antibody subclasses, epitopes, and geometries to provide a measure of FcγR (Fcγ receptor)-mediated functionality. IgG1 anti-Env titers diminished rapidly during antiretroviral therapy (ART; t1/2 3.0 ± 0.8 months), while the dimeric rsFcγRIIIa activity persisted longer (t1/2 33 ± 11 months), suggesting that there is maintenance of functional antibody specificities within the diminished pool of anti-HIV Env Abs. The initial antibody response to infection in two subjects was characterized by approximately fivefold higher FcγRIIIa compared with FcγRIIa binding activity. Uncoupling of FcγRIIa and FcγRIIIa activities may be a distinct feature of the early antibody response that preferentially engages FcγRIIIa-mediated effector functions. Two to three STI cycles, even with low viremia, were sufficient to boost dimeric FcγR activity in these seroconverter subjects. We hypothesize that increased humoral immunity induced by STI is a desirable functional outcome potentially achievable by therapeutic immunization during ART. We conclude that controlled viral antigen exposure under the protection of suppressive ART may be effective in eliciting FcγR-dependent function in support of viral reactivation and kill strategies.


ART; Fc receptor; anti-envelope antibody


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