Recent studies have suggested a key role of immunoglobulin (Ig) isotype distribution, Fc medicated functions, and memory immune response persistence in the development of a human immunodeficiency virus (HIV) vaccine. Following this, co-lead researchers Shixia Wang, Nicole L. Yates, and Justin Pollara and collaborators conducted a follow-up study on these parameters in a polyvalent DNA prime-protein boost HIV vaccine, PDPHV, which they had reported on previously.
Their article, published in NPJ Vaccines, stated that broadly reactive binding antibody and antibody-dependent cellular cytotoxicity (ADCC) responses, as well as durable envelope glycoprotein GP120 (gp120)-specific memory B cells, were induced by the PDPHV regimen. According to the authors, these supplementary findings, in addition to the favorable results observed in their previous trial, further supported PDPHV as a promising HIV vaccine candidate.
The investigators used IgG isotype and gp70-V1V2-binding enzyme-linked immunosorbent assay (ELISAs), peptide arrays, and ADCC assays to assess antibody responses to PDPHV among patients with HIV who volunteered to receive the study regimen. Additionally, a B-cell enzyme-linked immune absorbent spot (ELISPOT) assay was used to assess the presence of gp120-specific memory B-cells.
Based on their analysis, the authors stated that the gp120-specific antibodies were predominantly composed of the IgG1 isotype and demonstrated favorable ADCC responses. Furthermore, the team found that the 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.” Lastly, the B-cell ELISPOT analysis showed that the gp120-specific memory B-cells were present for at least six months following the patients’ last dose.
Overall, in combination with the initial PDPHV trial’s results, including “high titer antibody responses with broad specificity, neutralizing activities to multiple HIV-1 subtypes, as well as polyfunctional T cell responses,” the authors deemed that the PDPHV regimen continued to show promise as an emerging vaccine candidate for HIV.
Source: NPJ Vaccines