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Worcester HIV Vaccine (WHV) recently announced the forming of a Safety Monitoring Board (SMB) for the Phase 1b study WHV138. The board chair, Dr. Marnie Elizaga, is an infectious disease specialist with long working experience at the HIV Vaccine Trial Network (HVTN). The two other SMB members are co-chair Dr. Michael Keefer, Interim Chief of Infectious Diseases at University Rochester Medical School and Dr. Yunda Huang, faculty statistician and co-principal investigator of the HVTN Statistical and Data Management Center within the Fred Hutchinson Cancer Research Center (Fred Hutch). Dr. Sue Li, a consultant from Fred Hutch, is serving as a non-voting member of the SMB.

The SMB kick-off meeting was formally held on September 20th through a virtual conference and attended by the entire WHV 138 trial leadership, including the members of the Protocol Safety Review Team (PSRT), the principal investigators of the WHV138 study, the medical officer, and Data Coordinating Center (DCC) staff members. During the anticipated 2-year trial period, the SMB will meet periodically to review accumulated patient safety data and to make recommendations about the future conduct of the trial ensuring highest safety measures for all study participants.

The WHV138 trial started enrollment in early July 2021 and will evaluate the safety and immunogenicity of the vaccine product PDPHV, a polyvalent DNA-Protein HIV vaccine co-administered together in repeated doses over the course of 12 months in Group 1 and 8 months in Group 2. Results from this trial will further inform the vaccine development of the PDPHV candidate, with plans to optimize dose and administration regimens in a phase 2 trial currently under development.

With the enrollment of the phase 1b trial WHV138 recently launched, Worcester HIV Vaccine (WHV) has invited three highly experienced experts in HIV vaccine clinical studies to form a Safety Monitoring Board (SMB). The SMB will be advisory to the WHV138 Program and will be responsible for the continued safety of the study participants and the validity as well as scientific merit of the trial. The following three HIV vaccine experts constitute the trial’s SMB and will share their expertise and professional opinion during the conduct of this trial.

Dr. Marnie Elizaga is the chair of the SMB. She is a board-certified infectious disease specialist who served as the protocol team leader and medical monitor for numerous early phase clinical trials at the HIV Vaccine Trials Network (HVTN).  She is currently an independent consultant.

The Co-chair, Dr. Michael Keefer, is a board-certified infectious disease specialist with 30 years of experience in the field of preventative HIV vaccines. He currently is the Interim Chief of Infectious Diseases at the University of Rochester and the Principal Investigator of their HIV/AIDS Clinical Trials Unit, which works with the HVTN and AIDS Clinical Trials Group (ACTG). His wealth of knowledge will be a great contribution to the SMB.

Dr. Yunda Huang is a faculty statistician and Co-Principal Investigator of the HVTN Statistical and Data Management Center within the Fred Hutchinson Cancer Research Center and has provided statistical leadership for numerous HIV vaccine clinical trials. Her expertise as a biostatistician is highly valuable to the WHV138 trial.

The Worcester HIV Vaccine (WHV)’s Polyvalent DNA/Protein HIV Vaccine (PDPHV) formulation is composed of five DNA vaccine plasmids and four gp120 recombinant proteins.  PDPHV is the only vaccine formulation currently under clinical investigation that is covering viral Env antigens from all four major circulating HIV subtypes.  The phase 1a clinical study HVTN124 has been completed in a multi-center human study run by the HIV Vaccine Trial Network (HVTN). The initial results have demonstrated that PDPHV is very safe and highly immunogenic in humans which was reported at the HVTN Full Group Meeting in May 2021.

Recently, WHV conducted further analyses to compare the HVTN124 immunogenicity results to published results of other HIV vaccine trials conducted by the HVTN. In a number of immune response assays, the HVTN124 study, especially the DNA prime – protein boost arm, showed either higher response rates or higher magnitude than other reported HVTN studies. The immune response assays used were CD4+ T cell, Env-specific IgG, gp70-V1V2-specific IgG, ADCC (both against gp120-coated target cells or Infectious Molecular Clone (IMC) infected target cells) and neutralizing antibodies response against Tier 1B viruses. More significantly, the HVTN124 formulation elicited high breadth of immune responses against both autologous and heterologous HIV-1 Env antigens. The above data further validated the design of a polyvalent Env formulation delivered by a DNA/protein combination immunization approach to achieve the polyfunctional immune responses with cross-clade breadth.

A study conducted by Dr. Lu’s group at the University of Massachusetts Medical School (UMMS), recently published in Emerging Microbes & Infections (EMI), found that the PDPHV vaccine delivered as a DNA prime – Protein boost regimen elicited high levels of gp120-specific antibody secreting cells (ASC) and memory B cell responses.

Worcester HIV Vaccine (WHV) licensed the PDPHV product from UMMS three years ago to quickly advance this vaccine candidate through their product development program geared towards finding a safe and effective globally relevant HIV vaccine. This particular study, using the mouse model, evaluated different vaccination regimens of the polyvalent vaccine formulation consisting of a plasmid DNA component encoding for the HIV-1 envelop glycoprotein gp120 antigen and a recombinant gp120 protein matching the same gp120 DNA vaccine plasmid. The naked DNA vaccine was delivered by intramuscular injection in buffered saline. The gp120 protein vaccine was delivered in two different ways, with and without the adjuvant Alum. The study demonstrated that the immunization approach of DNA prime- protein boost was more effective in eliciting gp120-specific B cell response than using either the DNA or the protein vaccine alone. The data further show that by priming the immune system with the DNA vaccine, the need of including an adjuvant as part of the recombinant protein vaccine boost formulation is not as critical since the antigen-specific B cells are already activated by the DNA prime. Previously, Dr. Lu’s group also reported that gp120 DNA immunization was able to improve the T follicular helper (Tfh) cell responses and germinal center B cell development in mice but that study did not determine if the B cells were antigen-specific (read more here).

Although the DNA prime-protein boost vaccination approach has been widely used in preclinical and clinical studies especially in the field of HIV vaccine development, the exact role of DNA prime immunization has not been fully elucidated yet. Developing an effective HIV vaccine remains to be a major scientific challenge and these findings reported by Dr. Lu’s group that DNA priming plays a key role in stimulating antigen-specific B cell responses can have a major impact on the development of vaccines capable of inducing high quality and long-lasting antibody responses.

Below is the link of the recently published paper:

DNA priming immunization is more effective than recombinant protein vaccine in eliciting antigen-specific B cell responses (tandfonline.com)

Worcester HIV Vaccine (WHV) is happy to announce that the phase 1b clinical trial WHV138, evaluating the safety and immunogenicity of the vaccine product PDPHV-21401, has started screening last week with anticipated enrollment of the first patient this week.

WHV138 is a single-site clinical trial conducted at Brigham and Women’s Hospital, a teaching affiliate of Harvard Medical School in Boston, MA, and is building onto the positive results of the recently finished phase 1a HVTN124 trial that was managed by the HIV Vaccine Trial Network (HVTN). The phase 1b trial will further investigate the polyvalent DNA/gp120 vaccine candidate with a simplified administration schedule. WHV138 differs from the HVTN124 protocol in that the vaccine product will now be tested using a co-delivery regimen as opposed to a DNA prime – Protein boost approach. In particular, the study will explore two different simplified approaches: one with a reduced number of vaccinations by co-administering the DNA and the Protein/adjuvant GLA-SE products at the same time but in different arms; the other approach uses a mixture of DNA and Protein vaccines, omitting the use of GLA-SE.

“We are excited to start this clinical trial to investigate the development of a potential HIV vaccine relevant for global health,” said Stephen Walsh, MD, Principal Investigator of WHV138 and a physician in the Division of Infectious Diseases at Brigham and Women’s Hospital.

It is the first US FDA approved Investigational New Drug (IND) application for WHV, the sponsor of the clinical trial, allowing WHV to quickly advance the novel vaccine candidate PDPHV-21401 through their recently established product development program. This is truly a major milestone for WHV since the biotechnology company was only founded three years ago by licensing the HIV vaccine technology from Professor Shan Lu’s laboratory at the University of Massachusetts Medical School. 

“We are thrilled to see the fast progress of our HIV vaccine candidate PDPHV managed by WHV,” said Dr. Shan Lu. 

The clinical research organization Target Health, LLC, was responsible for the IND filing for WHV and will provide monitoring service for the WHV138 trial.  Waisman Biomanufacturing, a contract manufacturing organization based in Wisconsin, performed GMP manufacturing service for the polyvalent DNA/gp120 vaccine to be used in WHV138.  The adjuvant GLA-SE, used in the current formulation, was provided by IDRI in Seattle.  Detailed design of WHV138 can be found at clinicaltrials.gov.

The human immunogenicity of WHV’s investigational HIV vaccine candidate, PDPHV (Polyvalent DNA/Protein HIV Vaccine), is promising based on the recent phase 1 data reported at the Full Group Meeting of HIV Vaccine Trial Network (HVTN) in early May 2021.

PDPHV is composed of five DNA vaccine plasmids and four gp120 recombinant proteins. The DNA vaccines were used to prime the immune system (T cells and B cells) to receive a boost of HIV proteins, which signals the body to produce protective antibodies against HIV. PDPHV is the first and only vaccine formulation that includes viral Env antigens from all four major circulating HIV subtypes to advance to safety and immunogenicity studies in humans.

PDPHV completed its safety and immunogenicity testing in a Phase I clinical trial (HVTN 124) for healthy adult human volunteers 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 Institutes of Health (NIH). The mission of the HVTN is to fully characterize the safety, immunogenicity, and efficacy of HIV vaccine candidates with the goal of developing a safe, effective vaccine as rapidly as possible for prevention of HIV globally.

The HVTN 124 study team reported that PDPHV was safe and well tolerated in its full course of 18 months of study. No serious adverse event was observed. More significantly, the majority of HVTN 124 study participants who received the experimental PDPHV developed high level HIV specific CD4+ T cells and antibody responses across very diverse HIV subtypes. Such antibodies showed high levels of antibody dependent cellular cytotoxicity activity (a function of killing virus infected cells) and the ability to neutralize a wide range of Tier 1b HIV viral isolates in a laboratory-based assay.

“The immunogenicity data of HVTN 124 is remarkable” said Jim Kublin, MD., Executive Director of HVTN. “How to elicit strong immune responses and how to ensure such immune responses can be directed against diverse viral strains circulating in the world are two major challenges in the HIV vaccine field. PDPHV data showed great progress to address both questions.”

PDPHV was originally developed from Dr. Shan Lu’s laboratory at the University of Massachusetts Medical School. He received more than $50 million from NIAID/NIH to oversee the development and manufacturing of PDPHV. WHV licensed PDPHV from UMMS in early 2018 for its further clinical development. WHV is also establishing broad collaborations 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. WHV is also investing in producing additional supplies of PDPHV for more advanced human studies.

On May 6^th, Dr. Shan Lu gave a presentation on behalf of the HVTN124 protocol team during a plenary session that was part of the larger 2021 HVTN Full Group Meeting. He shared a summary of the excellent immunogenicity data obtained from the multi-center phase 1a study testing the investigational HIV vaccine candidate PDPHV, a polyvalent DNA/Protein HIV Vaccine. To read the whole press release, click on the link below.

It is our great pleasure to announce that Iris Benhayoun has joined our team as an independent consultant.  Iris will assist in WHVs HIV vaccine development including the upcoming WHV138 clinical trial study. 

Iris holds a Master of Science in Epidemiology from the University of Massachusetts Amherst and comes with an extensive background in trial studies. Most recently, Iris worked as a clinical research coordinator for both the Specialty Retina Center and the Specialty Gastro Center where she was responsible for patient recruitment and retention, as well as the preparation of clinical offices to comply with sponsor requirements for study site selections.

Previously, Iris worked at the Global HIV Vaccine Enterprise assisting in the Timely Topics in HIV Vaccine initiative. She helped create print and online guidance materials for researchers working on the development of a safe and effective HIV Vaccine.

Iris’ experience at the HIV Enterprise and in clinical trial studies makes her a perfect match for WHVs 138 trial and we are extremely excited to have her on board.