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Robust Antibody-Dependent Cellular Phagocytosis by monocytes plays a role in controlling HIV viremia in an acutely infected MSM cohort.

While broadly neutralizing antibodies against HIV have been shown to be important in HIV vaccine strategies, recent studies have shown that Fc mediated non-neutralizing antibodies are associated with protection against HIV and may play a role in the development of an antibody-based HIV vaccine. Here we investigated the functionality and kinetics of four Fc effector functions (Antibody-dependent neutrophil phagocytosis (ADNP), cellular phagocytosis (ADCP), complement deposition (ADCD) and Natural killer cell degranulation cytotoxicity (ADNK) in a longitudinal cohort of 53 largely MSM individuals in Coastal Kenya at 3 months, 1 year and 3.5-4 years post HIV acquisition. Additionally, using a standard neutralization assay and a global HIV pseudovirus panel, we tested for neutralizing ability 3.5-4 years post-HIV acquisition. Of the 53 participants, only 15 had detectable neutralizing activity. However, all the 4 Fc effector functions were detected in all individuals at all time points tested, with increasing activity over time. Nevertheless, only a few individuals (20) had high FC polyfunctionality. While Fc polyfunctionality was not associated with neutralizing ability, it was significantly associated with higher viremia at all the 3-time points tested. Of all Fc functions tested, only ADCP negatively correlated with viremia at 3 months post-HIV acquisition (rho= -0.46, p=0,0006). Our results show that Fc mediated functions arise early in HIV and can be sustained up to 4 years post HIV infection. Additionally, the low neutralization breadth confirms that evolution of broadly neutralizing antibodies against HIV is rare.

Author(s): Ian Oyaro1, Matt Gorman5, Galit Alter5, Eduard J. Sanders1, 3 Thumbi Ndung’u2, 4and Eunice Nduati1

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