WHV is pleased to announce the publication of the HVTN 124 clinical study report in The Lancet HIV. Study investigators led by HVTN 124 Protocol Chair Dr. Ian Frank of the Perelman School of Medicine of the University of Pennsylvania reported not only on the excellent safety profile of WHV’s polyvalent DNA/Protein HIV vaccine candidate (PDPHV), but also its unprecedented immunogenicity results in human volunteers who received PDPHV. The HVTN 124 trial was able to elicit strong and cross-reactive immune responses against several HIV subtypes by a number of immune parameters.
The randomized, placebo-controlled, double-blind phase 1a trial (ClinicalTrials.gov identifier: NCT03409276) was conducted across six US clinical sites between 2018 and 2020. The study was sponsored and managed by the HIV Vaccine Trials Network (HVTN), which is funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institute of Health (NIH).
Sixty volunteers were enrolled to test the current generation of PDPHV with two main components: a five-plasmid DNA vaccine (env A, B, C, A/E and gag C) in saline and a quadrivalent env (A, B, C, A/E) protein vaccine whose antigens are matched to the DNA vaccine and adjuvanted with GLA-SE. Both the DNA and protein/adjuvant vaccines were delivered by intramuscular injection.
The main study consisted of two groups: one Group tested the heterologous DNA prime and protein/adjuvant boost approach, and the other group tested co-administration of the DNA and protein/adjuvant vaccine administered at the same time but injected into different arms. Both groups received five vaccinations at months 0, 1, 3, 6 and 8.
Overall, the PDPHV formulation tested in HVTN124 was well tolerated and both vaccination regimens were found to be safe. More significantly, however, was the immunogenicity of the PDPHV vaccine strategy, which was found to be superior to many previous HIV vaccines in several ways:
- The investigators observed a high response rate (90% to 100%) and high magnitude of titer (>1:10,000) of serum antibody responses among vaccinees against a panel of gp120/p140 antigens from diverse HIV-1 subtypes.
- High level and cross-subtype antibody-dependent cellular cytotoxicity (ADCC) activities were found in most vaccinees as measured by an assay in which the target cells were transfected with infectious molecular clones (IMC). While such assay mimics a viral infection, many of the previous HIV vaccine studies did not elicit ADCC against IMC-transfected target cells.
- Moreover, PDPHV in HVTN 124 induced neutralizing antibody activities against relatively neutralizing resistant Tier 1B viruses across different subtypes (clades B, C, AE and AG) while previous HIV vaccine studies either did not elicit such neutralizing activities or their neutralizing titers were lower than the HVTN 124 sera against the same Tier 1B virus.
- PDPHV elicited high titer IgG responses in 67-100% of participants against gp70-V1V2 antigens from subtypes A, B, C, and AE, an established corelate of protection against HIV infection. The rate and magnitude of these responses exceeded those in previous HIV vaccine studies.
- Furthermore, all volunteers in the prime-boost group achieved 100% CD4+ T cell responses which has not been universally observed in previous human HIV vaccine studies.
Achieving such high immune responses with all of the above biomarkers in one HIV vaccine study is quite remarkable. Given the challenge of developing an efficacious HIV vaccine, it has always been a major objective to develop a vaccine which can elicit a wide spectrum of immune responses in order to maximize the chance of preventing HIV infection. The HVTN 124 study demonstrated that PDPHV is progress towards that objective. Advanced phase clinical trials are warranted to test the efficacy of PDPHV to prevent HIV acquisition.
Of note is that the prime-boost group in HVNT 124 seemed to consistently outperform the co-administration group with respect to response rates and/or magnitude for each immunologic outcome assayed. More basic immunology studies are required to fully understand the true mechanisms and differences of these two approaches.
The study team speculates that the broad and robust immune responses seen in HVTN 124 are a result of the matched prime-boost antigens and the polyvalent ENV antigen approach, a unique HIV vaccine design that originated in Dr. Shan Lu’s lab at the University of Massachusetts Chan Medical School (UMCMS). WHV licensed PDPHV IP from the UMCMS in 2018 and has been managing the product development program of this candidate vaccine.
The DNA and protein vaccines used in HVTN 124 were manufactured by Waisman Biomanufacturing, a contracted manufacturing organization, while the adjuvant was supplied by The Access to Advanced Health Institute (AAHI) who specifically formulated GLA-SE.
WHV is grateful for the HVTN 124 trial volunteers, as well as study clinicians, clinical staff, and lab scientists from all six clinical sites and the entire HVTN organization.
