Abstract
Since publishing our original reports on the safety and immunogenicity of a polyvalent DNA prime-protein boost HIV vaccine (PDPHV) which elicited high titer antibody responses with broad specificity, neutralizing activities to multiple HIV-1 subtypes, as well as poly-functional T cell responses, accumulated findings from other HIV vaccine studies indicated the important roles of Ig isotype distribution, Fc medicated functions and the persistence of memory immune responses which were not studied in previous PDPHV related reports. The current report provides further detailed characterization of these parameters in human volunteers receiving the PDPHV regimen. Antibody responses were assessed using IgG isotype and gp70-V1V2-binding ELISAs, peptide arrays, and antibody-dependent cellular cytotoxicity (ADCC) assays. B cell ELISPOT was used to detect gp120-specific memory B cells. Our results showed that the gp120-specific antibodies were primarily of the IgG1 isotype. HIV-1 envelope protein variable regions V1 and V2 were actively targeted by the antibodies as determined by specific binding to both peptide and V1V2-carrying scaffolds. The antibodies showed potent and broad ADCC responses. Finally, the B cell ELISPOT analysis demonstrated persistence of gp120-specific memory B cells for at least 6 months after the last dose. These data indicate that broadly reactive binding Abs and ADCC responses as well as durable gp120-specific memory B cells were elicited by the polyvalent heterologous prime-boost vaccination regimens and showed great promise as a candidate HIV vaccine.
Highlights
Development of a safe and effective vaccine is crucial for the control of the HIV pandemic
Detailed biomarker analysis of the RV144 trial showed that the gp70-V1V2-specific antibody responses and Fc-mediated antibody functions inversely correlated with the risk of infection while there were no broadly neutralizing antibodies detected in protected volunteers[6,11]
The current report expands the previous findings of high antibody titers elicited in phase 1 clinical trial DP6-001 of the polyvalent DNA prime-protein boost vaccine by demonstrating the breadth of these responses and their functionality
Summary
Development of a safe and effective vaccine is crucial for the control of the HIV pandemic. It became clear that candidate HIV vaccines may elicit immune protection via Fc-mediated antibody functions[6,7,8,9,10]. Detailed biomarker analysis of the RV144 trial showed that the gp70-V1V2-specific antibody responses and Fc-mediated antibody functions inversely correlated with the risk of infection while there were no broadly neutralizing antibodies (bNAbs) detected in protected volunteers[6,11]. This is an important finding because many previous HIV vaccine studies have only focused on bNAbs[12,13,14]
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