At the recent HIV Vaccine Trials Network (HVTN) Conference 2023 in Seattle, WA, and the International Society for Vaccines (ISV) 2023 Annual Congress in Lausanne, Switzerland, Worcester HIV Vaccine (WHV) presented exciting data of a novel CD4 binding site specific and cross-clade neutralizing human monoclonal antibody (HmAb) elicited by the first-generation PDPHV, a collaborative effort between WHV, Dr. Peter Kwong and Dr Tongqing Zhou from the NIH Vaccine Research Center (VRC) and Dr. Xiangpeng Kong and Dr. Kun-Wei Chan from New York University.
The research team isolated and characterized a novel CD4-binding site monoclonal antibody, HmAb64, from a DP6-001 trial volunteer who was immunized with PDPHV as a DNA prime – Protein boost regimen. On a VRC cross-clade panel of HIV-1 pseudo-virus strains, HmAb64 neutralized viruses across clades A, B, C and AE including tier-2 neutralization resistant strains. The cryo-EM structure of the antigen-binding fragment of HmAb64 indicated that the key interaction of HmAb64 is similar to the CD4-binding loop, a critical component of the CD4-binding site.
The vaccine elicitation of HIV-neutralizing antibodies with tier-2-neutralization breadth has been a challenge for several decades. Our findings represent a major step forward in the long effort to develop an effective HIV vaccine and indicates that PDPHV could be a strong vaccine candidate against HIV infection.
DP6-001 was a phase 1 trial testing the safety and immunogenicity of the first-generation PDPHV investigational product that originated from the lab of Dr. Shan Lu, Professor Emeritus at the University of Massachusetts Chan Medical School and Chief Scientific Officer at WHV. The design of this polyvalent gp120 subunit-based HIV vaccine candidate has since been improved and developed into the second-generation PDPHV, which has been tested in the phase 1a trial HVTN124 and the currently ongoing phase 1b trial WHV138. Immunogenicity studies from these trials are ongoing, including more human mAbs isolation research from HVTN124 to further investigate whether the second-generation PDPHV candidate is capable of eliciting similar or even better immune responses.
