Worcester HIV Vaccine

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WHV Joins the World in Commemorating World AIDS Day 2023

Today on World AIDS Day 2023, we at WHV reaffirm our commitment to help end the HIV pandemic and keep focus on our mission to create a safe and effective vaccine to prevent HIV infections around the world. We proudly reflect back on the progress made in our product development program of PDPHV this year and would like to take this opportunity to highlight a few key milestones while also thanking our devoted collaborators, funders and – perhaps most importantly – our trial volunteers without whom the research advancements would not be possible.

One very exciting milestone that will be reached within the next few weeks is the completion of WHV138, a single-site phase 1b study and WHV’s first sponsored trial testing the safety and immunogenicity of our investigational product PDPHV – a heterologous HIV vaccine candidate with a 5-plasmid DNA component and a matched quadrivalent Protein vaccine component. Our trial partners presented the progress of WHV138 at the 2023 ISV Annual Congress in Lausanne, Switzerland (read more) showing the vaccine regimen to be safe and well-tolerated. Preliminary data suggests that PDPHV is immunogenic, even in the study arm that received a co-administration of the DNA vaccine and the non-adjuvanted protein vaccine. These are intriguing results that will be explored further in studies to come.

During the past several months, WHV worked with a number of renowned researchers on cutting edge antibody isolation and characterization studies to get a more detailed understanding of the specific immune responses elicited by PDPHV, the polyvalent DNA/Protein HIV vaccine candidate pioneered and later improved by Dr. Shan Lu. Together with our collaborators at New York University and Uniformed Services University of the Health Sciences, we discovered that first-generation PDPHV elicited human monoclonal antibodies (HmAb) with attributes that are comparable to mAb induced by HIV infection. These remarkable findings were presented at three major conferences in the United States and Europe this year (read more here and here) and they keep our hopes high that PDPHV may be a strong vaccine candidate against HIV infection. We are thus currently working on additional antibody isolation projects induced by second-generation PDPHV under the phase 1a HVTN124 protocol. More studies are underway focusing on possible correlates of protection against HIV infection as well as immune response comparison analyses across HVTN124 and other HIV vaccine trial protocols.

We have to thank the world’s most eminent HIV vaccine researchers for such major collaborative efforts that not only support the PDPHV product development, but also advances the HIV vaccine research field as a whole. Dr Shan Lu, professor Emeritus at the University of Massachusetts Chan Medical School and Chief Scientific Officer at WHV, emphasizes the need for more collaboration: “We are here to support each other and work together. It is not you against me, it is us against HIV.” The recent past has shown us that accelerated vaccine development is possible when researchers and stakeholders join forces to achieve a common goal.  On this World AIDS Day 2023, let us be reminded that we all share a common goal: the development of an HIV vaccine that can eventually stop the spread of HIV worldwide. WHV is proud to take part in this mission with the support of our colleagues and the HIV vaccine research community.

WHV Celebrates 4-Year Anniversary

Four years ago, WHV was established as its founder Mr. Weibo Li signed a licensing agreement with the University of Massachusetts Chan Medical School (UMMS) to advance the development of PDPHV, a heterologous DNA/Protein HIV vaccine candidate that was created in the laboratory of Dr. Shan Lu. Soon after WHV was founded in early 2018, the phase 1a trial HVTN124 was launched in collaboration with the HIV Vaccine Trial Network (HVTN), testing the safety and immunogenicity of PDPHV. This six-site, randomized, placebo-controlled trial was completed early 2021 and showed excellent safety results and robust immunogenicity data which will soon be published. The 5-plasmid DNA – quadrivalent gp120 protein vaccine has since been advanced to the currently recruiting phase 1b trial WHV138, a single site trial testing various optimized vaccination schedules and anticipated to be completed in 2023.

Over the last four years, WHV established a dynamic and highly functional management system successfully running phase 2 grade vaccine products through CMOs, establishing a full quality control program, and submitting US FDA INDs leading to rapid progress of their clinical research program. 

This second generation PDPHV is currently the only HIV vaccine candidate tested in humans that not only covers the four major circulating subtypes of HIV strains, but also includes matched immunogens for the DNA and Protein vaccine components. All four Env antigens in PDPHV are from authentic viral sequences – a method that had never been done before in the history of HIV vaccine development. WHV is proud of their product development program holding significant promise for the HIV vaccine field, accelerating the development of a safe and effective preventative HIV vaccine with the possibility of global application.

This quickly advancing product development program is a testament of a major achievement for such a young biotech company.

WHV presents key data at 2022 Keystone Symposium on HIV Vaccines

Last week, the WHV team along with UMMS partners presented two posters at the Next Generation HIV Vaccines and Therapies conference held on March 27 – March 30, 2022 and organized by Keystone Symposia on Molecular and Cellular Biology.

One of the posters presented results from the phase 1a HVTN124 trial that tested WHV’s second generation polyvalent DNA/Protein HIV vaccine (PDPHV). In this trial, the investigational vaccine was overall safe and well tolerated.  PDPHV was highly immunogenic as shown by the high magnitude antibody responses against not only the four autologous Env antigens included in the vaccine formulation, but also a panel of 13 heterologous gp120/140 antigens from diverse viral subtypes and consensus Env antigens.  Such human IgG responses were detected in all vaccinated volunteers. In addition, everyone from the treatment group developed high magnitude antibody responses against diverse gp70 V1/V2 antigens. Moreover, positive functional activities of the immune responses were demonstrated by ADCC, neutralizing antibody, and CD4+ T cells, which were observed in almost all vaccinated volunteers but not in placebo controls.  These responses are highly cross reactive against viral targets from different subtypes. Notably, volunteers who received the DNA prime – Protein boost regimen showed higher level immune responses as compared to those who received the DNA/Protein co-administration regimen. For example, potent and cross-reactive ADCC activity was significantly higher the prime-boost regimen group. This group also showed Env-specific CD4+ T cells in all volunteers. At this point, it is not clear why the prime-boost regimen and the co-delivery regimen show such distinct differences in immune responses.

The other poster presented data of a study isolating an A32-like ADCC mediating monoclonal antibody (mAb) induced by the first generation PDPHV that was under investigation in the previous phase 1 trial DP6-001. This new mAb (HmAb78) showed cross-clade gp120 binding and potent ADCC activities. The magnitude of ADCC activity induced by HmAb78 reached the level of the gold standard mAb32, which was isolated from a chronically infected HIV-1 patient and serving as the ADCC benchmark in the HIV field, indicating that PDPHV is capable to induce an immune response similar to that induced by HIV infection. Another substantial finding was that HmAb78 shared the same Ig germline as that of A32. It is a highly significant finding for the HIV vaccine field that WHV’s candidate PDPHV can induce a potent ADCC mediating mAb similar to A32 generated from HIV infection.

The vaccine candidate PDPHV is currently the only product tested in humans that targets all four major circulating subtypes of HIV-1 responsible for the global HIV burden. Data presented at this year’s Keystone Symposium on HIV Vaccines provided much needed evidence to move PDPHV to more advanced research studies.

IRB approval to study memory B cell responses elicited by PDPHV

Dr. Lu has received IRB approval from the University of Massachusetts Chan Medical School (UMMS) to conduct ancillary antibody analyses using PBMC samples from the phase 1a HVTN 124 trial. This new research study, conducted in Dr. Lu’s lab at UMMS, will use B cell ELISPOT assay to better understand the dynamics of gp120-specific memory B cell responses elicited by WHV’s vaccine candidate PDPHV through the course of immunizations in HVTN 124.

Results from this study will inform the mechanisms for potent antibody responses against HIV-1 antigens used in the formulation of PDPHV and further help with the design of WHV’s product development program, including the design of future Phase 2 studies. New data resulting from this ancillary antibody study can provide very useful insights to the HIV vaccine field as the memory B cell development is pivotal for maintenance of serological memories after receiving the HIV vaccines.

WHV’s vaccine product PDPHV is a second-generation HIV-1 vaccine candidate that has shown excellent safety and immunogenicity results in the phase 1a trial HVTN 124 and is currently being tested in the phase 1b WHV138 trial to further study the vaccine safety and immunogenicity profile under a modified vaccination schedule. The polyvalent DNA/Protein HIV vaccine candidate consists of a 5-plasmid env (A, B, C, A/E) / gag (C) DNA vaccine and a 4-valent gp120 (A, B, C, A/E) Protein vaccine co-Administered with or without Adjuvant GLA-SE.

New Analyses of First Generation PDPHV show Broadly Binding and Functional Antibody and Persisting Memory B cell Responses in Humans

A new research paper by WHV and the University of Massachusetts Chan Medical School scientists was recently accepted in NPj Vaccines, an open access journal by Nature Publishing Group. The study, led by Dr. Shan Lu, analyzed samples from the phase 1 DP6-001 trial to further characterize the specific immune responses elicited by the first-generation HIV vaccine candidate PDPHV and found that the gp120-specific antibodies were primarily of the IgG1 isotype, a finding that is consistent with other HIV vaccine studies. Furthermore, HIV-1 envelope protein variable regions V1 and V2 were actively targeted by the antibodies as determined by specific binding to both peptide and V1V2-carrying scaffolds. The antibodies showed potent and broad ADCC responses. In addition, the B cell ELISPOT analysis demonstrated persistence of gp120-specific memory B cells for at least 6 months after the last dose. This long-lasting, high level memory response as elicited by PDPHV has so far not been reported in any other HIV-1 vaccine trial.  It was found that non-persistent immune responses in RV144 trial may have contributed to low level of protection against HIV infection in study volunteers.

These new findings indicate that the polyvalent heterologous prime-boost vaccination regimen – using the first generation PDPHV candidate – was able to elicit broadly reactive binding antibodies and ADCC responses as well as durable gp120-specific memory B cells in humans. The formulation of this vaccine has since been improved by selecting the most optimal ENV variants based on the screening of a large panel of viruses (Wang, et al. 2017), forming the second generation PDPHV candidate that has since been tested in the phase 1a trial HVTN124 and is currently under investigation in the phase 1b WHV138 trial. Immunogenicity analyses of the second generation PDPHV candidate are ongoing for HVTN124 samples and results from the first batch of analyses will be published in the near future.

WHV 138 Phase 1b Clinical Trial Continues with the Recruitment of Group 2

As the recruitment of WHV 138 of Group 1 was recently completed with the enrollment of the 21st study participant, the clinical team resumes the recruitment of the phase 1b trial and started screening patients for Group 2. The vaccination regimen of Group 2 differs from the first group in that Group 2 participants will receive five vaccinations as opposed to four, but over the course of eight months instead of twelve months. While the investigational HIV vaccine candidate PDPHV is the same for both groups, Group 1 participants receive the DNA and Protein vaccine products separately in two different arms – the protein vaccine admixed with the adjuvant GLA-SE, while participants of Group 2 receive a DNA+Protein mix without the adjuvant.

WHV 138 is a phase 1b randomized double-blinded placebo-controlled trial evaluating the safety and immunogenicity of the polyvalent DNA/Protein HIV Vaccine (PDPHV) candidate, the first and only vaccine formulation tested in clinical trials that includes viral ENV antigens from all four major circulating HIV clades A, B, C, and AE. This product was previously tested in the HVTN 124 phase 1a trial and has shown excellent safety and immunogenicity results. It is now tested WHV 138 with a simplified vaccination regimen and will further be tested in a phase 2 trial to finalize the design of vaccine dosing and scheduling.

FDA Clears Worcester HIV Vaccine Investigational New Drug Application for Vaccine to Prevent HIV Infections

Worcester HIV Vaccine (WHV) has received clearance from the U.S. Food and Drug Administration for its Investigational New Drug (IND) application for a novel polyvalent DNA/prime-protein boost vaccine to prevent HIV, called PDPHV. The IND calls for the Worcester-based start-up to explore different vaccination designs in a phase 1b clinical trial to be launched in February 2021. A phase II clinical trial is expected to follow.

Based on discoveries by Shan Lu, MD, PhD, professor of medicine, and licensed from UMass Medical School, WHV’s vaccine employs a polyvalent DNA-prime/protein-boost technology to target multiple subtypes of HIV-1. PDPHV is a novel vaccine composed of five DNA plasmids and four gp120 recombinant proteins. The DNA component is used to prime the immune system to receive a boost of HIV proteins, which stimulate the body to produce potent antibodies against HIV.

“In a little over two years since the founding of WHV, we have filed our first IND. This is a major achievement and a true milestone for WHV,” said Yegor Voronin, PhD, chief operating officer of WHV. “The excellent safety results of PDPHV and positive preliminary immunogenicity data we have from earlier clinical trials give us confidence to rapidly develop our own clinical program.”

An earlier version of this vaccine was tested in a single-site clinical trial conducted at UMass Medical School, and the second generation of the vaccine has been recently tested at six US sites by the HIV Vaccine Trials Network (HVTN) under protocol HVTN 124. HVTN is funded by the National Institute of Allergy and Infectious Diseases (NIAID). Dr. James Kublin, Executive Director of HVTN, commented on the news: “I am very encouraged by the safety data and preliminary immunogenicity results of the HVTN124 trial and excited to see WHV’s further progress in advancing this promising vaccine candidate.”

PDPHV is the first and only vaccine formulation that includes natural viral antigens from all four major circulating HIV subtypes to advance to safety and efficacy trials in humans. Full immunogenicity results from HVTN 124 will be released later this year.

Over the last two decades, Dr. Lu’s lab has received more than $50 million in NIAID funding to oversee the development and manufacturing of PDPHV. WHV licensed PDPHV from UMass Medical School in early 2018 for development.

WHV has worked with Waisman Biomanufacturing, a contracted manufacturing organization, to use their proprietary technology to manufacture DNA plasmids with purer quality and higher yields than previously. Recently, Target Health, LLC, a New York-based CRO with many years of regulatory experience, joined the WHV team to help prepare and file the IND.

WHV is also collaborating with the Infectious Disease Research Institute (IDRI) in Seattle, which developed and manufactured the adjuvant used to stimulate responses to the protein component of the PDPHV vaccine. Adjuvants can be broadly leveraged to develop vaccines against many viruses, and are components of several COVID-19 vaccine candidates to broaden and lengthen the duration of protection against the SARS-CoV-2 virus.

“HIV remains a leading infectious cause of death worldwide, and is one of the most challenging viruses to protect against with a vaccine,” said Corey Casper, M.D., chief executive officer of IDRI. “IDRI is excited to contribute its immune-enhancing adjuvant, GLA-SE — with a proven safety and immunogenicity profile in thousands of humans to date — to this critical vaccine effort.”

2021-01-27-WHV-IND-clearedDownload

Drs. Lu and Voronin are interviewed by MassTERi

Dr. Lu and Dr. Voronin spoke with Anna Wortman and Dr. Karthik Dhatchinamoorthy from MassTERi about their experience in launching and running the Worcester HIV Vaccine.

MassTERi is an Entrepreneurship Club bringing together UMMS students and postdocs interested in pursuing careers in biotech and pharmaceutical industry. The conversation centered on the skills and personal qualities needed to succeed in industry, as well as on the current trend in biotech and pharma to use geographically distributed workforce and the challenges and opportunities of this approach.

Read the full interview here or download it as pdf by clicking below.

2020-07-08-MassTERi-interviewDownload

WHV Poised to Move Novel HIV Vaccine Through Clinical Development

Collaboration with UMMS Allows for Faster, More Effective Path to Advancing Clinical Trials

[DECEMBER 1, 2019]  ̶  This World AIDS Day researchers at Worcester HIV Vaccine (WHV), a biotechnology organization next to the University of Massachusetts Medical School (UMMS) announced plans to take their innovative HIV vaccine candidate through to Phase IIa clinical testing.  If proven immunogenic, this would be the first and only vaccine candidate that targets all four major HIV subtypes to advance to safety and efficacy trials in humans.

“A safe and effective HIV vaccine has the potential to shape the future course of this epidemic,” said Shan Lu, M.D., Ph.D., professor of Medicine at UMMS and the creator of WHV’s HIV vaccine. “Despite significant progress on the potential of new biomedical strategies in the global HIV response, we are still seeing more than 37 million people living with HIV around the world, and another 1.7 million newly infected each year. We know an effective vaccine to prevent HIV would be one of the biggest advances in global health.”

WHV’s investigational HIV vaccine candidate, PDPHV is in formative stages of development.  It is comprised of five DNA plasmids and four gp120 recombinant proteins and is being tested in healthy adult volunteers in a Phase I clinical trial (HVTN 124) run by the National Institute of Allergy and Infectious Diseases’ (NIAID) HIV Vaccine Trials Network (HVTN).  Immunogenicity results from the HVTN 124 trial are expected in early 2020 having just concluded all vaccinations in October.

“We are making excellent progress in preparing for the Phase IIa clinical trial of PDPHV – something that could happen as early as mid-2020, should the Phase I results show positive immunogenicity,” said Yegor Voronin, Ph.D., chief operating officer of WHV.  “We’ve done the hard work of advancing GMP manufacturing, optimizing the clinical trial design, and clarifying the regulatory pathway, all in an effort to move Phase IIa study as quickly as possible should we see a positive signal.”

Earlier this year, WHV researchers showed that they can improve the manufacturing of the DNA component of PDPHV and confirmed that its proteins continue to demonstrate an excellent stability profile, which will allow a faster and more effective path to Phase II clinical trials. 

Shan Lu and his group at UMMS have been working for more than two decades to advance a preventive HIV vaccine.  The PDPHV vaccine combines HIV DNA, which is used to prime the immune system to receive a boost of HIV protein, which signals the body to produce antibodies against HIV. This prime-boost approach activates both antibody and cell-mediated immune responses, and induces functional antibodies with better qualities and longevity than using either type of vaccine alone as shown by an earlier version of this vaccine in a single-site clinical trial conducted at UMMS.

Much of WHV’s progress in early research and development has been the result of collaborations with UMMS. In the last decade, Dr. Lu’s group at UMass Medical School received more than $30 million to oversee the development and manufacturing of PDPHV, which allowed WHV to license PDPHV from UMMS in early 2018 for its further development.  WHV has worked with Waisman Biomanufacturing (WB), a third party contracted manufacturing organization, to use  DH5a E. coli strain with WB’s proprietary technology, to manufacture DNA plasmids with purer quality and higher yields than previous cell lines. WHV is also establishing broad collaboration with academic and industry partners including the UMMS Mass Spectrometry Facility, led by Scott Shaffer, Ph.D., to develop new analytical assays to use during vaccine manufacturing.     This world AIDS Day as the global HIV community reflects upon its accomplishments, and takes stock of the challenges that lie ahead, WHV renews its commitment to rapidly and efficiently advancing a novel HIV vaccine through clinical development.  There’s no doubt that a safe and effective HIV vaccine is an essential component to ending the HIV epidemic once and for all.