Worcester HIV Vaccine

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HVTN 124 study conclusion supports advancement to WHV 138 clinical trial

The HVTN 124 clinical trial is wrapping up while the stability of the used vaccines is confirmed.

HVTN 124 is a phase 1 clinical trial conducted by NIH-funded HIV Vaccine Trials Network, testing the safety and immunogenicity of PDPHV-201401, WHV’s preventive HIV vaccine candidate. The trial has now been formally concluded with the lock of the database. Volunteers and researchers will be unblinded to the treatment group assignment in the near future. The preliminary data from the peak immunogenicity analyses are very encouraging  and support the advancement of this vaccine candidate to further clinical testing. The data will be presented at the HVTN’s annual 2021 Full Group Meeting on May 5-7, 2021.

Working with Waisman Biomanufacturing, WHV also formally completed the studies initiated by Dr. Shan Lu’s laboratory at UMass as part of the IPCAVD program to test the stability of all vaccine components used in the HVTN 124 trial. The results of these studies indicate that DNA vaccine, gp120 Env recombinant protein vaccine, and the GLA-SE adjuvant are all stable after 4-5 years and can be used in the planned WHV 138 clinical trial. To support the use of these vaccines in the WHV 138 trial, WHV extended the stability studies for all components.

WHV to present HVTN 124 results at the HVTN Full Group meeting

Safety and immunogenicity results from the HVTN 124 study will be presented by WHV at the Full Group meeting of HVTN.

HVTN 124 is a phase 1 clinical trial conducted by NIH-funded HIV Vaccine Trials Network, testing the safety and immunogenicity of PDPHV-201401, WHV’s preventive HIV vaccine candidate. The trial recently completed and immunogenicity is being assessed by both HVTN and WHV. The preliminary data from these analyses supports the advancement of this vaccine candidate to further clinical testing.

HVTN leadership invited WHV to present the results of the trial at its annual 2021 Full Group Meeting. The meeting will be held virtually on May 5-7, 2021 and will cover the progress in immune-mediated HIV prevention approaches including vaccines and passive immunizations.

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

Mireya Wesselossky joins WHV as Medical Officer

In preparation for its upcoming launch of a Phase 1b clinical trial, WHV engaged a well-known expert Dr. Mireya Wesselossky as our Medical Officer.

To follow up on the HVTN 124 phase 1 clinical trial, WHV is preparing to launch a phase 1b clinical trial WHV138 to further explore the safety and immunogenicity of its polyvalent PDPHV vaccine candidate. Different administration approaches and schedules will be explored in that study and the company is preparing to file an IND with the US FDA in the near future. As a Medical Officer, Dr. Wesselossky will join the Protocol Leadership team and will oversee the regular safety reports in WHV 138.

Dr. Wesselossky has been Associate Professor of Medicine at University of Massachusetts Medical School and an Infectious Disease Attending Physician at UMass Memorial Health Care since 2001. She has extensive experience with HIV, previously working with a >700 HIV-infected patients in the HIV Associated Neurocognitive Disorders (HAND) cohort in Central Massachusetts. In January 2018, she participated in opening a walk-in clinic in AIDS Project Worcester to diagnose, treat, and prevent many infectious disease conditions including sexual transmitted diseases, HIV, and HCV in a population with no easy access to medical care due to extreme poor socio-economic status.

Dr Wesselossky’s experience and unique strengths as an infectious diseases clinician and researcher will be invaluable for the conduct of the WHV 138 trial.

WHV Reaffirms Commitment to Advance Development of Novel HIV Vaccine

As the world commemorates World AIDS Day this week and grapples with a second pandemic in COVID-19, Worcester HIV Vaccine (WHV) reaffirms its commitment to developing a preventive vaccine to reduce HIV infections around the world as it advances its candidate vaccine toward more safety and efficacy trials. 

“The progress we have made this year is remarkable, especially considering the challenges posed by the COVID-19 pandemic,” said Yegor Voronin, Ph.D., chief operating officer of WHV.  “The fact that we stand poised to advance our HIV vaccine candidate to additional safety and efficacy testing is a testament to our commitment to developing a vaccine to protect against one of the world’s most elusive viruses.”

WHV’s investigational HIV vaccine candidate, PDPHV, is completing safety and immunogenicity testing in a Phase I clinical trial (HVTN 124) sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, and conducted by the NIAID-funded HIV Vaccine Trials Network (HVTN).  If proven immunogenic, PDPHV would be the first and only vaccine formulation that includes viral Env antigens from all four major circulating HIV subtypes to advance to safety and efficacy trials in humans. Immunogenicity results are being analyzed and will be shared in early 2021.

Earlier this year, WHV announced plans to investigate the dynamics of the immune responses seen in the HVTN124 trial, and conduct additional testing to better assess the breadth and potency of antibodies elicited by the PDPHV vaccine candidate, which will be critical to advancing vaccine manufacturing, and to planning further clinical trials.

PDPHV is a nucleic acid vaccine composed of five DNA plasmids and four gp120 recombinant proteins. The DNA vaccine is used to prime the immune system to receive a boost of HIV proteins, which stimulate the body to produce antibodies against HIV.  WHV researchers have optimized the manufacturing of the DNA component of PDPHV in the last two years and are continuing to ensure the gp120 proteins remain stable throughout the development process, all while setting a clear path toward regulatory review.  WHV is expected to file a new Investigational New Drug Application (IND) to the U.S. Food and Drug Administration (FDA) for PDPHV before the end of 2020 in partnership with Target Health, LLC, a New York-based CRO with many years of regulatory experience.

“The work we are doing to understand the types of immune responses induced by PDPHV is not only important to the HIV field, but is yielding important insights for the development of nucleic acid vaccines, which are also being tested for the novel SARS CoV-2 virus,” said Shan Lu, M.D., Ph.D., professor of Medicine at UMMS, who created PDPHV and who is also conducting COVID-19 vaccine research.  “We know that science—and an effective vaccine—requires us to persist, to test every concept, to be innovative and fearless in our discovery efforts, to find new ways of working together, and to persevere.  The recent progress of mRNA-based COVID-19 vaccines, which is another type of nucleic acid vaccine similar to DNA vaccines, just proved that this technology platform has very promising potential.”

Much of WHV’s progress in early research and development has been the result of collaborations within UMass Medical School (UMMS). In the last two decades, Dr. Lu’s group at UMMS received more than $50 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 is also establishing broad collaboration with academic and industry partners including the Infectious Disease Research Institute (IDRI) in Seattle, Washington, which developed and manufactured the adjuvant used to stimulate responses to the protein component of the PDPHV vaccine.  This World AIDS Day, we thank our HIV researchers, many who are now working on COVID-19 and are bringing valuable lessons to accelerate the discovery of preventive measures and treatments for COVID-19 while continuing to set the stage for an HIV vaccine.

2020-WHV-World-AIDS-Day-ReleaseDownload

Mollie Ockene returns as an intern

Senior at Middlebury College in Vermont, Mollie worked as an intern at WHV during the summer months. She provided valuable assistance in editing and formatting important documents, including research papers, sections of WHV’s IND application, and internal records.

She is now returning to WHV and will continue working on a variety of projects and learning various aspects of clinical vaccine development in a biotech environment.

A major step for the polyvalent HIV vaccine – WHV manufactures world’s first four-valent gp120 protein vaccine

Working with Waisman Biomanufacturing, WHV scientists manufactured a novel 4-valent gp120 protein vaccine for further clinical testing of its preventive HIV vaccine candidate PDPHV.

Previously, the laboratory of Dr. Shan Lu at the University of Massachusetts Medical School (UMMS)  developed the polyvalent HIV vaccine including both DNA and protein components.  In recently conducted phase I clinical trial HVTN124 supported by US NIH/NIAID, four gp120 proteins from the four major clades of HIV-1 (A, B, C, and AE) were individually vialed. The proteins had to be mixed with each other and with the GLA-SE adjuvant at bedside prior to administration.

Recently, WHV has launched a major program to establish the production of a final drug product with 4 gp120 proteins mixed in the same vial.  Extensive pilot tests were conducted to ensure the proteins can be formulated together and characterized using existing and new analytical assays.  WHV consulted with US FDA and received confirmation on its plans to ensure the quality of this novel product. 

Now for the first time in the history of HIV vaccine development, four highly purified gp120 proteins were mixed in equal amounts to produce the 4-valent protein mixture, which was vialed to produce the final product to be used in the upcoming clinical trials.

This novel 4-valent formulation will greatly simplify storage, transportation, and administration of the protein vaccine. WHV recently produced a new batch of the 5-valent DNA component of the vaccine using the updated manufacturing process.  Having both DNA and protein vaccine components positions WHV for rapid advancement toward the next stages of clinical testing of the PDPHV vaccine candidate.

GLA-SE adjuvant remains stable after four years

Dr. Shan Lu’s laboratory working with the Infectious Disease Research Institute (IDRI) completed another test as part of the stability program for its GLA-SE adjuvant manufactured in 2016. The results show the adjuvant is very stable and can be used in more clinical trials.

PDPHV vaccine candidate was developed in the laboratory of Dr. Shan Lu at the University of Massachusetts Medical School (UMMS). In 2015, using the funding provided by NIAID’s IPCAVD program, IDRI manufactured the adjuvant specifically for PDPHV vaccine as part of the HVTN 124 clinical trial. At the time, a 4-year program was launched to monitor the stability of GLA-SE to support its continued use in the clinical trial. With the pending completion of HVTN124, the 48-month time point stability data review showed no noticeable degradation of the product.

WHV will use the remaining GLA-SE in more WHV planned clinical studies. Accordingly, WHV will work with IDRI to extend the stability study to further monitor the preservation of this adjuvant.

End of the five-year program demonstrates stability of WHV’s DNA vaccine

Dr. Shan Lu’s laboratory working with Waisman Biomanufacturing and Eurofins completed the stability program for its DNA vaccine manufactured in 2015. The results show vaccine is very stable and can be used in clinical trials.

PDPHV vaccine candidate was developed in the laboratory of Dr. Shan Lu at the University of Massachusetts Medical School (UMMS). In 2015, using the funding provided by NIAID’s IPCAVD program, the laboratory manufactured the DNA vaccine to be used in the HVTN 124 clinical trial. At the time, a 5-year program was launched to monitor the stability of the five-valent vaccine to support its continued use in the clinical trial. The program recently ended, and the data review showed no noticeable degradation of the product.

WHV will use the remaining DNA product in its planned Phase 1 study. In parallel, it will extend the stability study to further monitor the preservation of this DNA vaccine.

WHV advances to manufacture 4-valent protein for Phase 2a trial

Working with Waisman Biomanufacturing, WHV demonstrated that protein bulk drug substances manufactured in 2015 remain stable and will advance to formulating them into a 4-valent drug product for the first time.

Recombinant gp120 proteins from HIV-1 clades A, B, C, and AE were manufactured in 2015 at Waisman Biomanufacturing in Madison, WI with support from NIAID’s Integrated Preclinical/Clinical AIDS Vaccine Development (IPCAVD) program. At the time, some of the proteins were vialed individually as Final Drug Product for use in the Phase clinical trial HVTN 124. The trial completed vaccinations in October of 2019 and demonstrated good safety profile (the immunogenicity data are expected in early 2021).

The remaining bulk drug substances have been stored at -70C degree. Now, WHV and Waisman Biomanufacturing tested the proteins and found them to be stable and potent, supporting the decision to formulate the proteins into a Final Drug Product to be used in the planned Phase 2a clinical trial.

For the first time, the proteins will be formulated as a 4-valent mixture, greatly simplifying storage and administration of the vaccine. WHV and Waisman Biomanufacturing already defined release and stability assays to be used to characterize and monitor the 4-valent mixture. The US Food and Drug Administration (FDA) was consulted regarding the proposed plans and provided positive feedback for WHV’s plans.