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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]

Zika virus (ZIKV) is an emerging pathogen that causes devastating congenital defects. The overlapping epidemiology and immunologic cross-reactivity between ZIKV and dengue virus (DENV) pose complex challenges to vaccine design, given the potential for antibody-dependent enhancement of disease. Therefore, classification of ZIKV-specific antibody targets is of notable value. From a ZIKV-infected rhesus macaque, we identify ZIKV-reactive B cells and isolate potent neutralizing monoclonal antibodies (mAbs) with no cross-reactivity to DENV. We group these mAbs into four distinct antigenic groups targeting ZIKV-specific cross-protomer epitopes on the envelope glycoprotein. Co-crystal structures of representative mAbs in complex with ZIKV envelope glycoprotein reveal envelope-dimer epitope and unique dimer-dimer epitope targeting. All four specificities are serologically identified in convalescent humans following ZIKV infection, and representative mAbs from all four groups protect against ZIKV replication in mice. These results provide key insights into ZIKV-specific antigenicity and have implications for ZIKV vaccine, diagnostic, and therapeutic development. [Display omitted] • Using whole ZIKV as a probe, we identify potent ZIKV-specific neutralizing antibodies • Neutralizing mAbs target four distinct epitopes at the E dimer-dimer interface • The four ZIKV-specific epitopes are prevalent in ZIKV infection in humans • mAbs from all four antigenic groups provide protection against ZIKV infection Sankhala et al. use Zika virus as a bait to identify potent neutralizing monoclonal antibodies (mAbs) that are highly specific to Zika virus. These mAbs bind conformational epitopes across the virion dimer-dimer interface and provide protection against infection in a mouse Zika virus challenge model. [ABSTRACT FROM AUTHOR]

Genus Flavivirus , which includes 53 virus species, is the leading cause of arthropod-borne diseases in humans. Diagnosis of these viral diseases is complicated by their overlapping epidemiology and clinical manifestations, and the fact that cross-reactive antibody responses are frequently elicited by individuals in response to infection. We developed a bead-based immunoassay to concomitantly profile the isotype and subclass of antibody responses (five isotypes and four subclasses) in parallel with specificity against multiple antigens. Our panel included 22 envelope (E) and non-structural 1 (NS1) proteins of different flaviviruses (Zika (ZIKV), Dengue (DENV), Yellow Fever (YFV), West Nile (WNV), Japanese Encephalitis (JEV) and Tick-Borne Encephalitis (TBEV)) and the envelope protein of Chikungunya virus (CHIKV). Using 54 samples from 40 individuals with ZIKV infection that had been pre-characterized, we identified 1) stronger ZIKV responses in individuals previously exposed to flavivirus compared to flavivirus-naïve individuals; 2) different antibody isotypes depending on the stage of infection: acute, convalescent and late convalescent; 3) cross-reactive responses; and 4) a potential CHIKV infection. The assay had a broad dynamic range (>5 logs) and has the potential to distinguish antigen-specific responses induced by ZIKV infection from cross-reactive responses. The multidimensional data provided by this high-throughput antibody-profiling platform can advance our understanding of the human immune response to flaviviruses as they expand their global reach. • We developed a bead-based multiplex immunoassay to profile human antibody responses. • Antibody responses against 21 flavivirus E and NS1 antigens and one Chikungunya virus antigen are detected simultaneously. • The assay requires a small volume of sample (20 μl) and has a large dynamic range (>5 logs). [ABSTRACT FROM AUTHOR]