Publications & Reports

Boosting of markers of FcgammaR function in anti-HIV antibodies during structured treatment interruption.

Billings H, Wines B, Dyer W, Center R, Trist HM, Kent SJ, Hogarth PM
Burnet Institute, 104125, Melbourne, Victoria, Australia ; hugh.billings@gmail.com.

Abstract

Anti-HIV envelope antibodies elicit important Fc receptor functions, including FcgammaRIIIa-mediated NK killing of opsonised 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 rsFcgammaR binding assays combine effects of opsonising antibody subclasses, epitopes and geometries to provide a measure of FcgammaR-mediated functionality. IgG1 anti-Env titres diminished rapidly during ART (t1/2 3.0 +/- 0.8 months), while the dimeric rsFcgammaRIIIa activity persisted longer (t1/2 33 +/- 11 months), suggesting 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 characterised by ~five-fold higher FcgammaRIIIa compared to FcgammaRIIa binding activity. Uncoupling of FcgammaRIIa and FcgammaRIIIa activities may be a distinct feature of the early antibody response that preferentially engages FcgammaRIIIa mediated effector functions. Two to three STI cycles, even with low viremia, were sufficient to boost dimeric FcgammaR activity in these SC subjects. We hypothesise that increased humoral immunity induced by STI is a desirable functional outcome potentially achievable by therapeutic immunisation during ART. We conclude that controlled viral antigen exposure under the protection of suppressive ART may be effective in eliciting FcgammaR dependent function in support of viral reactivation and kill strategies.

Link to publisher’s web site

Publication

  • Journal: AIDS Research and Human Retroviruses
  • Published: 10/07/2019
  • Volume: Epub ahead of print

Authors