Last week, the WHV team along with UMMS partners presented two posters at the Next Generation HIV Vaccines and Therapies conference held on March 27 – March 30, 2022 and organized by Keystone Symposia on Molecular and Cellular Biology.
One of the posters presented results from the phase 1a HVTN124 trial that tested WHV’s second generation polyvalent DNA/Protein HIV vaccine (PDPHV). In this trial, the investigational vaccine was overall safe and well tolerated. PDPHV was highly immunogenic as shown by the high magnitude antibody responses against not only the four autologous Env antigens included in the vaccine formulation, but also a panel of 13 heterologous gp120/140 antigens from diverse viral subtypes and consensus Env antigens. Such human IgG responses were detected in all vaccinated volunteers. In addition, everyone from the treatment group developed high magnitude antibody responses against diverse gp70 V1/V2 antigens. Moreover, positive functional activities of the immune responses were demonstrated by ADCC, neutralizing antibody, and CD4+ T cells, which were observed in almost all vaccinated volunteers but not in placebo controls. These responses are highly cross reactive against viral targets from different subtypes. Notably, volunteers who received the DNA prime – Protein boost regimen showed higher level immune responses as compared to those who received the DNA/Protein co-administration regimen. For example, potent and cross-reactive ADCC activity was significantly higher the prime-boost regimen group. This group also showed Env-specific CD4+ T cells in all volunteers. At this point, it is not clear why the prime-boost regimen and the co-delivery regimen show such distinct differences in immune responses.
The other poster presented data of a study isolating an A32-like ADCC mediating monoclonal antibody (mAb) induced by the first generation PDPHV that was under investigation in the previous phase 1 trial DP6-001. This new mAb (HmAb78) showed cross-clade gp120 binding and potent ADCC activities. The magnitude of ADCC activity induced by HmAb78 reached the level of the gold standard mAb32, which was isolated from a chronically infected HIV-1 patient and serving as the ADCC benchmark in the HIV field, indicating that PDPHV is capable to induce an immune response similar to that induced by HIV infection. Another substantial finding was that HmAb78 shared the same Ig germline as that of A32. It is a highly significant finding for the HIV vaccine field that WHV’s candidate PDPHV can induce a potent ADCC mediating mAb similar to A32 generated from HIV infection.
The vaccine candidate PDPHV is currently the only product tested in humans that targets all four major circulating subtypes of HIV-1 responsible for the global HIV burden. Data presented at this year’s Keystone Symposium on HIV Vaccines provided much needed evidence to move PDPHV to more advanced research studies.
