Our first generation vaccine candidate has been tested at the University of Massachusetts Medical School in a phase 1 clinical trial DP6-001. The current, second-generation, candidate PDPHV-201401 was tested in a phase 1a clinical trial HVTN 124 conducted by the NIH-sponsored HIV Vaccine Trials Network (HVTN). The phase 1b trial WHV 138 launched in 2021 and will further explore the administration of the vaccine components to optimize immune responses. Phase 2a trial WHV 238 is under development and will focus on identifying optimal vaccine formulation and administration schedule to be tested in a Phase 2b efficacy trial. Read more about our trials below.
WHV 138 Trial – Phase 1b
Building on the positive results from the HVTN 124 trial, WHV 138 Phase 1b trial will explore simplified administration of the vaccine. Group 1 will explore the safety and immunogenicity of DNA and adjuvanted protein administered at different sites for four immunizations over the course of 12 months. Group 2 will explore the safety and immunogenicity of the DNA and protein mixed and administered together without the adjuvant for five immunizations over the course of 8 months.
The trial started recruiting in July 2021 and completed enrollment in May 2022. The trial is ongoing.
ClinicalTrials.gov Identifier: NCT04927585
HVTN 124 Trial – Phase 1a
The second generation of the vaccine, PDPHV-201401, recently completed testing in a Phase I trial HVTN 124. The trial explored the safety and the immunogenicity of the vaccine candidate. It also compared the sequential 3 DNA-prime plus 2 protein-boost administration to five simultaneous administrations of DNA and protein at different sites. Learn more about our Vaccine Approach.
HVTN 124 protocol opened on March 16, 2018, the vaccinations were completed on October 16, 2019, and preliminary immunogenicity data analyses were presented at the HVTN Full Group Meeting in May 2021.
ClinicalTrials.gov Identifier: NCT03409276
DP6-001 Trial – Phase 1 (first generation PDPHV)
The DP6-001 Phase I clinical trial was conducted in 2004-2006 to test the safety and immunogenicity of the first generation of the polyvalent DNA-prime/protein-boost vaccine. This initial formulation was based on the limited number of primary isolates of HIV-1 available in the 1990s and used QS-21 as an adjuvant.
ClinicalTrials.gov Identifier: NCT00061243
Binding antibody titers
In the groups receiving low doses of DNA, most volunteers had undetectable levels of Env-specific antibody responses after 3 DNA immunizations. However, the antibody titers rose quickly after just one protein boost. The anti-gp120 IgG titers reached levels comparable to those observed in chronically infected HIV patients (i.e. 1:105 or higher). By the end of the trial at week 52, participants in group B maintained significant levels of serum anti-gp120 IgG titers. Furthermore, Western blot analysis revealed that antibodies were broadly reactive against a wide range of 11 heterologous primary HIV-1 gp120 antigens (Wang, 2008).
Virus neutralization activity
A study of antibody neutralization activity found high-titer nAb responses in all vaccinated volunteers’ sera against 3 sensitive Tier 1A viruses. Testing the sera against a panel of 11 heterologous primary viruses from subtypes A to E revealed that a majority of volunteers had positive Nab activities against at least half of the pseudotyped viruses expressing primary Env antigens (Wang, 2008). The levels of neutralization were higher than what was reported in previous literature with different HIV vaccine designs that included a DNA component.
ADCC activity
Antibody-dependent cellular cytotoxicity (ADCC) is an important function of antibodies that allows efficient killing of infected cells. A panel of human mAbs was isolated from DP6-001 volunteers and showed potent and broadly reactive ADCC activities (Costa, 2016). In addition, ADCC activities were identified in sera from selected DP6-001 volunteers and the titer increased following each immunization. Further studies are planned to analyze the serum ADCC activities with the entire DP6-001 volunteer population.
T cell immunity
The vaccine also elicited cell-mediated immunity in the volunteers. Overall, 83-100% of volunteers had positive Env-specific IFN-γ responses that were mediated predominantly by polyfunctional CD4+ T cells (Bansal, 2008). HIV-1 specific CD8+ T cell responses were also detected in the high dose group, but at a lower frequency.