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The heterologous HIV vaccine candidate PDPHV – currently tested in phase 1b WHV138 – recently completed the stability program for both its main components, the 5-plasmid DNA vaccine and the 4-valent recombinant gp120 Protein vaccine. The DNA vaccine was manufactured in 2015 and has proven to remain stable for 8 years. The 4 separate Protein lots from HIV-1 clades A, B, C, and AE, which are mixed at bedside into a single 4-valent vaccine, recently successfully completed the final stability testing after 6.5 years since the beginning of the stability program in 2016. Both of these products were previously used for the phase 1a HVTN124 trial.  The remarkable stability profile of PDPHV is the best evidence showing WHV’s high quality GMP manufacturing and QC/QA programs.  WHV would like to thank their contracted manufacturing partner Waisman Biomanufacturing (WB) for such high quality vaccine products.

For the soon to be conducted phase 2a study, new lots of each of the components of PDPHV have already been produced at WB.  A further optimized protein vaccine vialing method was successfully implemented to allow for a simplified vaccine dispensing of the four gp120 Protein vaccine components as a single pre-mixed Drug Product (DP). It is no longer needed to mix the 4-valent protein vaccine at bedside. For the DNA vaccine component, a new lot was produced with substantial improvements in yield and purity as compared to the previously produced product. The formulations of both the DNA and the Protein vaccines did not change and after thorough consultation, the FDA provided positive feedback regarding WHV’s plans to use the newly manufactured DPs for PDPHV’s advancing product development program. The stability program of both DPs is off to a great start: The new DNA product has recently passed its third year of stability testing and the recombinant 4-valent pre-mix Protein vaccine recently passed its second year of stability testing. Both products will continue the stability program until the upcoming phase 2a in-human trial is completed.

WHV is excited to announce that we are approaching the end of our phase 1b WHV138 trial as all Group 1 participants have now completed their scheduled visits and the remaining Group 2 participants continue the study until their final 12-month follow-up visit, with the last volunteer’s last visit to be expected by December of this year.

Overall, the safety profile of the vaccine candidate PDPHV looks excellent. The trial has passed all three SMB safety reviews without any concerns. Immunogenicity studies will be performed after the trial is fully completed, but preliminary analyses look very promising and reflect the remarkable immunogenicity data from the previous HVTN124 trial – the phase 1a trial testing PDPHV under a slightly different vaccination regimen. Results from that study will be published in the near future.

The second generation PDPHV is a polyvalent HIV vaccine candidate with two main components: a 5-plasmid DNA vaccine (ENV clades A, B, C, and AE and gag-C) and a recombinant quadrivalent gp120 Protein vaccine with antigens matched to the DNA vaccine. These two components have been investigated as a DNA prime/Protein boost regimen in HVTN124 and co-administered together both with and without adjuvant in WHV138. The forthcoming phase 2a trial will further explore the best form of regimen, vaccination schedule and dosing.

WHV138 is currently the only in-human trial investigating a vaccine candidate targeting viral ENV antigens from the four major circulating HIV-1 subtypes. Based on the results from HVTN124, we believe that PDPHV has the potential to be a globally relevant HIV vaccine candidate.

Last month, the WHV team along with partners from the University of Massachusetts Chan Medical School (UMMS) presented two posters at the Keystone Symposia on HIV Vaccines.

The first poster presented data of an A32-like ADCC mediating monoclonal antibody (mAb) isolated from a donor who participated in UMMS’ phase 1 trial DP6-001 testing the safety and immunogenicity of the first generation PDPHV. The new mAb (HmAb78) has previously been shown to have cross-clade gp120 binding and potent ADCC activities comparable to A32, a potent mAb isolated from a chronically infected HIV-1 patient that serves as an ADCC benchmark for non-neutralizing mAb in the HIV field – indicating that PDPHV is capable to induce an immune response similar to that induced by HIV infection. More significantly, HmAb78 used the same germline as A32. The new data presented at this year’s Keystone HIV Vaccine meeting is a crystal structure of HmAb78 which showed that the antigen binding site was largely identical to that of A32. This work was done in collaboration with Dr. Marzena Pazgier and her postdoctoral fellow Dr. William D. Tolbert from the Department of Medicine of Uniformed Services University of the Health Sciences. Dr. Xiangpeng Kong from New York University (NYU) also played an important role in this study. These findings further confirm that WHV’s polyvalent gp120 DNA /Protein HIV vaccine targets critical viral epitopes which may be important for HIV infection. 

The second poster presented the recently determined structure and epitope of the CD4-binding site (CD4bs) human mAb HmAb64, which has also been isolated from a donor who participated in the DP6-001 trial and neutralized multiple primary HIV-1 subtypes. Through cryogenic electron microscopy, the collaborating research team at NYU (Dr. Xiangpeng Kong and Dr. Kun-Wei Chan) provided a detailed structure of HmAb64 and specifically discovered a binding mode that is distinct from known CD4bs-specific neutralizing antibodies (nAbs). These new findings can not only help with immunogen design for HIV prevention research but also provide additional evidence that PDPHV may be a strong vaccine candidate against HIV infection.

The second generation PDPHV is currently tested in phase 1b WHV138 to be concluded by the end of this year and WHV eagerly pursues to move this promising HIV vaccine candidate to more advanced in-human trials.

The WHV138 Safety Monitoring Board recently held their third periodic safety review meeting and concluded that the investigational HIV vaccine candidate PDPHV does not present any safety concerns to the trial participants. The trial can thus continue as planned without any modification.

This was the last scheduled safety review meeting for WHV’s phase 1b trial, which is already in its final stage: All active volunteers have completed their vaccination visits and are within their 12-month observation period. About a third of the Group 1 participants have already finished the trial with their final study visit. The last volunteer’s last visit is expected to take place towards the end of this year. Blood samples for immunogenicity studies are collected through the final study visit to allow for longevity analyses of the induced immune responses up until 12 months after final vaccination.

WHV’s second-generation HIV vaccine candidate PDPHV includes a 5-pladmid DNA vaccine component with a matched quadrivalent gp120 Protein vaccine component and is currently the only vaccine formulation targeting viral ENV antigens from all four major circulating HIV subtypes. With such a low-risk safety profile and promising immunogenicity results, WHV is excited to be moving PDPHV through the subsequent product development stages as the phase 1b trial WHV138 is coming to an end.

Alongside leading HIV vaccine researchers, WHV joined the quest for a safe and effective HIV vaccine in 2018, when the small biotech company was founded in Worcester, MA by licensing the intellectual property for the vaccine candidate PDPHV from Dr. Lu’s lab at the University of Massachusetts Chan Medical School. Since then, WHV has successfully undertaken a major product development campaign for the heterologous 5-plasmid DNA, quadrivalent gp120 protein vaccine and became the IND holder of the currently ongoing phase 1b trial WHV138. On HIV Vaccine Awareness Day 2023, we would like to recognize and thank the many volunteers of our trials, our clinical partners, investors, and renowned HIV experts on our team, without which the accomplishments of our vaccine development program would not be possible.

We at WHV are hopeful that PDPHV – targeting multiple subtypes of HIV-1 – can advance the HIV vaccine field towards finding a globally relevant, safe and effective HIV vaccine. Based on recent exploratory studies, WHV’s investigational product may be capable of eliciting immune responses that haven’t been seen since the RV144 trial. These remarkable preliminary immunogenicity data are resulting from the previously conducted HVTN124 trial, a phase 1a trial testing the safety and immunogenicity of PDPHV in a DNA prime – Protein boost approach. Preparations for efficacy trials to further confirm these preliminary data are in progress and will be conducted as soon as partnerships are established.

As Bill Clinton has declared over 25 years ago, “only a truly effective, preventive HIV vaccine can limit and eventually eliminate the threat of AIDS.” We at WHV are honored to participate in this mission and are eager to continue until the end of the HIV pandemic is accomplished.

Last week, our phase 1b trial WHV138 has reached a new milestone: The first enrolled volunteer has completed the trial with their final study visit, two years after trial enrollment.

This Group 1 participant has received four vaccinations with the heterologous HIV vaccine candidate PDPHV over the course of 12 months, followed by a 12-month safety observation period. All trial volunteers are expected to complete the trial within the next several months, with the very final visit in Group 2 to be expected by December of this year.

WHV is grateful for all volunteers’ commitment in participating in this early research phase of PDPHV. Without them, advancement in HIV vaccine science would not be possible. PDPHV is currently the only HIV Vaccine candidate tested in humans using a 5-plasmid DNA vaccine combined with matched antigens in the quadrivalent Protein vaccine component. If proven to be efficacious, PDPHV may be a promising vaccine candidate in the utilization as an HIV prevention method worldwide. Preparations to advance PDPHV into a phase 2 research study are ongoing.

The phase 1b WHV138 Safety Review Board (SMB) recently held their second of three period safety review meetings. The board chair, Dr. Marnie Elizaga, together with board members, Dr. Michael Keefer and Dr. Yunda Huang, as well as our study statistician Dr. Sue Li, reviewed cumulative safety data unblinded as to treatment/placebo arm and concluded that the trial can continue without any modifications based on the low-risk safety data. Overall, the trial is progressing well and already in its final stage, the 12-month post-final vaccination follow-up period. With the recent administration of the trial’s final vaccination, the third milestone for the next periodic safety review by the SMB has been met and will be conducted within the next couple of months.

After about a year and half since trial initiation, the WHV138 clinical team has recently administered the trial’s final vaccination of the investigational product PDPHV, a polyvalent DNA/Protein HIV Vaccine that includes five DNA plasmids encoding for HIV Env A, B, C, AE and gag C with matched protein gp120 Env antigens. WHV138 is currently the only in-human clinical trial testing a heterologous HIV vaccine candidate that targets all four major circulating subtypes of HIV-1. The administration of the trial’s final vaccination without the occurrence of any major safety concerns thus far is therefore a promising and exiting milestone for the whole HIV vaccine research community.

The single-site, randomized, placebo-controlled phase 1b trial WHV138 started screening in June of 2021 and enrolled a total of 42 volunteers into two groups. Both groups received the DNA and the Protein products of PDPHV as a co-administration regimen in repeated doses but at slightly different vaccination schedules. While Group 1 volunteers received four doses of the DNA and the adjuvanted Protein vaccine in two different arms over the course of twelve months, Group 2 volunteers received five doses of a mix of the DNA and the Protein vaccine without an adjuvant into both arms over the course of eight months. All active volunteers will continue the trial for a 12-month safety observation period following their final vaccination.

The previously conducted phase 1a HVTN124 trial assessed the safety and immunogenicity of PDPHV using a DNA prime – Protein boost approach which has shown remarkable immune responses according to preliminary analyses that were presented at the 2022 Keystone Symposium on Next Generation HIV Vaccines and Therapies earlier last year. Exploratory immunogenicity studies of WHV138 will be conducted once the trial concludes towards the end of this year.

United with people around the world in the fight against HIV, we at WHV reaffirm our commitment to help end the HIV pandemic with our continued efforts in developing a safe and effective HIV vaccine to significantly reduce new infections around the world. Today, the WHV team celebrates the achievements of the HIV vaccine research community in 2022 by reflecting on our accomplishments during the past 12 months:

WHV’s greatest pride this year is the progress of the phase 1b WHV138 trial, a single-site randomized controlled trial testing the safety and immunogenicity of the polyvalent DNA/Protein HIV Vaccine candidate (PDPHV) in two different treatment groups using a co-administration regimen in repeated doses. As the IND-holder of PDPHV, WHV successfully filed their first IND annual report with the FDA and passed the Safety Monitoring Board review without any safety concerns. After successfully concluding enrollment of 42 healthy volunteers in the midst of the COVID-19 pandemic, WHV138 is now approaching the finishing line in volunteer vaccinations which is followed by a 12-month safety follow-up period.

PDPHV is currently the only vaccine tested in humans with a formulation consisting of DNA-encoded gp120 antigens of four different clades (A, B, C, and AE) and matched recombinant gp120 proteins. This heterologous HIV vaccine candidate has shown promising results using a DNA prime – Protein boost regimen in the preceding phase 1a HVTN124 trial, a multi-center randomized controlled trial sponsored by the HIV Vaccine Trials Network (HVTN) and funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH). Secondary analyses of HVTN124 indicate that PDPHV has the potential to elicit cross-protective, high magnitude, and large breadth immune responses. Therefore, WHV strives to quickly advance the product development program of PDPHV and has begun planning a phase 2 trial to further investigate the immunogenicity of this promising vaccine candidate. With such a low-risk safety profile and very positive preliminary immunogenicity results, PDPHV could play a major role in the worldwide HIV prevention efforts since a safe and effective preventative HIV vaccine is one of the necessary tools to control the HIV pandemic.

In addition to the clinical trial’s progress, WHV was able to help advance the HIV vaccine field by contributing to the growing body of knowledge with complex research studies resulting from WHV’s vaccine development program.  With the support of renowned research partners, three different posters featuring the first- and second-generation PDPHV were presented at two major conferences this year. Two poster presentations were held at the 2022 Keystone Symposium on HIV Vaccines in March and two posters were presented at the 2022 ISV Annual Congress in September. Moreover, at the recent HVTN Full Group Meeting held in Seattle, WA in October,  HVTN124 immunogenicity data were presented in a comparison analysis across multiple HVTN studies, focusing on possible correlates of protection against HIV infection. This exploratory analysis suggests that PDPHV has the strongest potential at achieving higher levels of antibody responses than any other vaccine candidate tested so far.

These preliminary data are an encouraging note that with PDPHV, the HIV vaccine field has a vaccine candidate in the pipeline with great promise to potentially be protective against HIV infection. However, additional extensive research is required to further explore these observations – a challenge that WHV and their partners are excited to dive into.

Another big milestone reached earlier this year is WHV’s move to a new research facility to accommodate their quickly progressing vaccine development program. Previously using M2D2 incubator space at the University of Massachusetts Chan Medica School (UMCMS) in Worcester, MA, where PDPHV originated from Dr. Shan Lu’s lab, WHV is now operating at a new location with much larger space and independent from UMCMS to further develop their research work.

Most recently, the WHV team was graciously welcomed into the International AIDS Society (IAS) Corporate Partnership Program as a Bronze member for the coming year. It is an honor for WHV to be working alongside world-leading HIV vaccine experts who have also joined this multi-stakeholder group that is aiming to support industry’s contribution to HIV vaccine R&D. Together, we hope to address the ongoing critical need to accelerate the development of a safe and effective HIV vaccine that can eventually be used for our ultimate goal: The prevention of new HIV infections worldwide.

About a year since the WHV138 trial initiation, the fourth and final vaccination was recently administered to the last volunteer of Group 1, marking a major milestone for WHV’s first phase 1b trial. Group 1 volunteers receive a co-administration of the polyvalent DNA/Protein HIV vaccine PDPHV over the course of 12 months, with the DNA and adjuvanted Protein vaccine injected intramuscularly in different arms at month 0, month 3, month 6 and month 12. This 4-dose vaccination regimen uses one dose less than the 5-dose vaccination regimen previously tested in the phase 1a trial HVTN124, in which the 5 doses were completed over the course of 8 months instead of 12. By comparing HVTN124 with WHV138, researchers are trying to assess if volunteers in WHV138 can achieve the same high level immunogenicity responses as observed in HVTN124.

Following their final vaccination, all actively enrolled volunteers are monitored for a 12-month follow-up period to ensure the safety of all study participants. The recent safety review conducted by the WHV138 Safety Monitoring Board did not identify any safety concerns.

WHV138 is a single-site randomized placebo-controlled phase 1b trial assessing the safety and immunogenicity of the second generation PDPHV, a polyvalent HIV vaccine candidate that originates from Dr. Lu’s lab at the University of Massachusetts Chan Medical School in Worcester, Massachusetts. This investigational vaccine has previously been tested under a different vaccination schedule using a DNA prime – protein boost approach in the phase 1a HVTN124 trial, which was sponsored by the HIV Vaccine Trials Network (HVTN) and funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH).

Analyses from the preceding trial HVTN124 have shown excellent safety results and very promising immunogenicity data – remarkable findings that will be published soon.