A recent publication in Emerging Microbes & Infections organized by NIH supported HIV Vaccine Trial Network (HVTN) compared the immune responses observed in 13 different HIV vaccine trials, including 3 efficacy trials, and found that the polyvalent DNA prime with matched polyvalent protein/GLA-SE boost regimen of HVTN124, testing WHV’s vaccine candidate PDPHV, elicited the most robust and broad IgG and IgG3 V1V2 binding antibody and CD4+ T cell responses amongst all other regimens. In recent literature, these vaccine induced responses have been considered as “immune corelates of protection” implying that any protective HIV vaccine would need to elicit such responses.
The paper is a large collaborative research effort among many leading HIV vaccine study experts. Of the 34 analyzed different vaccine regimens included in those 13 trials, immune responses induced by PDPHV were amongst the highest across all vaccination regimens analyzed. The DNA prime – protein boost arm of HVTN124 showed the highest median breadth scores of binding antibody responses and also 100% response rate for IgG binding antibody responses to gp70 V1V2, as well as 100% response rate and high magnitude for CD4+ T-cell responses. More impressively, the DNA prime – protein boost in HVTN124 was the only regimen raising high level IgG3 antibody responses against gp70 V1V2 among all the regimens included in the study.
The perhaps most significant finding is that some of these antibody responses induced by PDPHV were remarkably higher in magnitude than those seen in the Thai trial RV144, the only regimen that has demonstrated modest efficacy to date. PDPHV’s unique attribute of a polyvalent DNA prime with matched polyvalent protein boost vaccine design is also thought to have resulted in better binding and cellular immune responses than those observed in the two most recent efficacy trials HVTN 702 and 705.
These results not only confirm that the DNA prime with matched protein boost approach is a promising HIV vaccine design but also put it in a relative scale against other HIV vaccine designs of the last two decades. This very valuable comparative analysis supports to test PDPHV in more advanced clinical trials to meet the great need of an efficacious HIV vaccine for the global health.
