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

Abstract

Anti-HIV envelope (Env) antibodies elicit important Fc receptor functions, including FccRIIIa-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 rsFccR binding assays combine effects of opsonizing antibody subclasses, epitopes, and geometries to provide a measure of FccR (Fcc receptor)-mediated functionality. IgG1 anti-Env titers diminished rapidly during antiretroviral therapy (ART; t 1/2 3.0-0.8 months), while the dimeric rsFccRIIIa activity persisted longer (t 1/2 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 FccRIIIa compared with FccRIIa binding activity. Uncoupling of FccRIIa and FccRIIIa activities may be a distinct feature of the early antibody response that preferentially engages FccRIIIa-mediated effector functions. Two to three STI cycles, even with low viremia, were sufficient to boost dimeric FccR 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 FccR-dependent function in support of viral reactivation and kill strategies.

Identification of peptide epitopes of the gp120 protein of HIV-1 capable of inducing cellular and humoral immunity

“…However, there are no long-term antibody protection findings in immunized patients. 57 Studies are needed to verify the protection that peptide-specific antibodies can provide against HIV infection. Furthermore, finding an increment of IgG in groups of immunized mice in serum suggests that a systemic response against peptides is being achieved, this is also important since these antibodies could act against the spread of the virus to the lymph nodes.…”