Worcester HIV Vaccine

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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.

World AIDS Day 2021 – WHV is committed to help end the HIV pandemic

Today, WHV joins the world in commemorating World AIDS Day in remembrance of those who have lost their lives due to AIDS-related illness and to show support for those living with HIV. This world AIDS day, we reflect back on the achievements of the HIV vaccine research community in 2021 and acknowledge the ongoing critical need to accelerate the development of a safe and effective HIV vaccine in order to reduce HIV infections around the world.

Over the past year, WHV has accomplished two major clinical development milestones relevant for the fight against HIV: In March of 2021, the phase 1a HVTN124 trial evaluating the safety and immunogenicity of WHV’s polyvalent DNA/Protein HIV Vaccine (PDPHV) candidate formally concluded without the occurrence of any safety concerns and secondary analyses showed remarkable immunogenicity data. This trial was sponsored by the the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), and conducted by the NIAID-funded HIV Vaccine Trials Network (HVTN). Results from HVTN124 were presented at the HVTN Full Group Meeting in May. Only a few months later in July, the subsequent phase 1b WHV138 trial was launched, aiming to further characterize the safety and immunogenicity profile of PDPHV in a simplified vaccination schedule. This is the first time for WHV to act as the sponsor of a clinical trial since the biotech company was established only three years ago. WHV138 is already half-way enrolled and is anticipated to conclude in the Fall of 2023. Plans for a phase 2 trial are already underway as WHV prepares to move the vaccine candidate into the next testing stage.

There is growing evidence that a safe and effective as well as globally relevant HIV vaccine needs to not only be multigenic, polyvalent, and heterologous, but also be able to elicit a multi-factorial immune response in order curb the HIV pandemic manifesting a large HIV-1 subtype diversity. 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. Its formulation is based on decades of research conducted by Dr. Lu’s lab at the University of Massachusetts Medical School (UMMS) in Worcester, MA. The vaccine consists of a 5-plasmid Env (A, B, C, E)/Gag (C)-expressing DNA vaccine and a recombinant gp120 protein vaccine of which the antigens are matched to the DNA plasmids. Results from Dr. Lu’s pre-clinical studies in rabbits, as well as early phase trials in humans indicate that when used in a DNA/Protein prime-boost regimen, PDPHV has the potential to elicit cross-protective, high magnitude and large breadth immune responses. With such a low-risk safety profile and very promising immunogenicity results, the vaccine candidate PDPHV could have a major impact on the HIV vaccine field, advancing it further towards developing a safe and effective HIV vaccine that can be applied worldwide.

WHV is honored to engage with a number of stakeholders joining efforts in ending the HIV pandemic that has caused hundreds of thousands of deaths and is still affecting millions of people today. Together with leading HIV vaccine researchers and renowned infectious disease specialists, WHV strives to advance the HIV vaccine field and aspires that AIDS will one day be a vaccine preventable disease.

WHV138 phase 1b clinical trial completed enrollment of Group 1

In less than 4 months since the start of the WHV138 trial, the clinical team enrolled 21 healthy volunteers into the study and thus completed the enrollment objective of the first of two groups. Now that Group 1 is fully enrolled, the clinical team will continue their screening efforts and start enrollment of Group 2 soon, anticipating to fully enroll the whole study by early 2022.

WHV138 is a phase 1b single site randomized placebo-controlled trial evaluating the safety and immunogenicity of the polyvalent DNA/Protein HIV vaccine product PDPHV, which is tested in two groups receiving two different vaccine regimens. Group 1 receives the DNA and Protein+adjuvant vaccines injected separately in each upper arm; 4 doses are given over the course of 12 months. Group 2 will receive the DNA and Protein products mixed together without the inclusion of an adjuvant; 5 doses are given over the course of 8 months. Both groups will be followed up for an additional 12 months to monitor the safety profile of the PDPHV product.

The PDPHV vaccine candidate consists of two components, a 5-plasmid DNA vaccine covering the HIV clades A, B, C, and AE, and a 4-valent recombinant gp120 protein vaccine, matched to the DNA plasmids. PDPHV is the first and only vaccine formulation tested in clinical trials that includes viral ENV antigens from all four major circulating HIV clades, presenting a vaccine candidate that could have a significant impact on the global HIV burden.  This product was previously tested in the HVTN124 phase 1a trial and has shown excellent safety and immunogenicity results. It is now tested with a revised vaccination regimen and will further be tested in a phase 2 trial to finalize the design of vaccine dosing and scheduling.

The WHV138 Safety Monitoring Board is formally constituted

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.

The Safety Monitoring Board for the Phase 1 b WHV138 Trial is Announced

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.

Polyfunctional Immune Responses Elicited by WHV’s Polyvalent DNA/Protein HIV Vaccine Formulation

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.