Mosaic vaccine-induced antibody-dependent cellular phagocytosis associated with delayed HIV-1 viral load rebound post treatment interruption.

A heterologous Ad26/MVA vaccine was given prior to an analytic treatment interruption (ATI) in people living with HIV-1 (mainly CRF01_AE) who initiated antiretroviral treatment (ART) during acute HIV-1. We investigate the impact of Ad26/MVA vaccination on antibody (Ab)-mediated immune responses and their effect on time to viral rebound. The vaccine mainly triggers vaccine-matched binding Abs while, upon viral rebound post ATI, infection-specific CRF01_AE binding Abs increase in all participants. Binding Abs are not associated with time to viral rebound. The Ad26/MVA mosaic vaccine profile consists of correlated non-CRF01_AE binding Ab and Fc effector features, with strong Ab-dependent cellular phagocytosis (ADCP) responses. CRF01_AE-specific ADCP responses (measured either prior to or post ATI) are significantly higher in individuals with delayed viral rebound. Our results suggest that vaccines eliciting cross-reactive responses with circulating viruses in a target population could be beneficial and that ADCP responses may play a role in viral control post treatment interruption. [Display omitted] • The mosaic vaccine triggers vaccine-matched antibody binding responses in PLWH • Infection-specific CRF01_AE responses are not further stimulated by vaccination • Binding antibodies are not associated with time to rebound upon ATI • Vaccine-induced ADCP responses associate with delayed viral rebound Mdluli et al. analyze antibody-mediated responses in participants who received the Ad26/MVA mosaic vaccine before an analytic treatment interruption (ATI). Mosaic vaccination elicits antibody binding responses to multiple subtypes but did not optimally boost the infection-specific CRF01_AE responses. High ADCP responses associate with delayed viral rebound upon ATI. [ABSTRACT FROM AUTHOR]