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.
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.
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.
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.
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.
WHV is proud to join the Massachusetts Medical Device Development Center (M2D2), a biotech incubator located at the University of Massachusetts Medical School in Worcester, MA.
M2D2 is a highly successful accelerator and incubator, which over the years supported more than 100 small companies. It is sponsored by 15 partner organizations, including major pharmaceutical and medical devices companies such as Johnson & Johnson, Boston Scientific, and Amgen.
The 1,200 square foot facility in Worcester opened in 2018 and is the newest of the three M2D2 locations. It includes open concept lab space with a range of shared equipment as well as conference rooms and offices. M2D2 companies receive access to and preferred rates for nearly 50 state-of-the-art core facilities at the UMMS and Lowell campuses. Mentoring program provides companies with advice on IP, corporate structure, deal-making, therapeutic areas, product development, and commercialization.
In joining M2D2, WHV is planning to take full advantage of the various facilities and UMMS resources being made available through this program and to further strengthen its operational capacity and scientific excellence.
WHV researchers believe in the need to train the next generation of leaders to tackle health challenges around the world. Thus, it is our great pleasure to announce that Mollie Ockene joined our team as an intern looking to learn more about HIV vaccine development and to assist with a variety of projects at the company.
Mollie is a rising senior from Boston studying Environmental Policy, Global Health, and pre-medical sciences. At Middlebury College in Vermont she gained experience as a volunteer EMT, joined the leadership board of her sailing team, and is the president of Middlebury Nutrition Outreach and Mentorship, a student organization focused on community engagement with local youth. She has also served on the Environmental Advisory Committee and worked as a research assistant for professors there.
Mollie spent last fall in New Zealand sailing on a tall ship, studying climate science and the health impacts of climate change on the local Māori population. Her academic interests focus on the intersection between medicine and social issues, making her particularly interested in our mission of developing a vaccine to prevent HIV infections worldwide.
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.
WHV cleared the path toward filing its own IND and hired Target Health to assist with preparing and filing the necessary documents with US FDA.
WHV is preparing to file a new IND for PDPHV, its investigational DNA-prime/protein-boost vaccine. PDPHV is comprised of five DNA plasmids and four gp120 recombinant proteins and is being tested in a Phase I clinical trial (HVTN 124) as a prime-boost regimen or co-administered in repeated doses, in healthy adult volunteers. Results of the HVTN 124 trial are expected in the next several months.
The Division of AIDS (DAIDS) of the National Institutes of Allergy and Infectious Diseases (NIAID) holds the current IND for the vaccine candidate and NIAID-supported HVTN is running the Phase I HVTN 124 trial. DAIDS expressed support for WHV’s plans to file its own IND and will facilitate the process by transferring several key documents to WHV.
Target Health, LLC, a New York-based CRO with many years of regulatory experience, joined the WHV team and will assist in preparing and filing the IND with the US FDA.
HVTN approved WHV proposal to conduct an exploratory study to better characterize the immune responses observed in volunteers in the HVTN 124 clinical study testing WHV’s PDPHV vaccine candidate.
HIV Vaccine Trials Network is conducting immunogenicity assays to assess the peak immune responses observed two weeks after the last immunization in the HVTN 124 trial. At the same time, WHV plans to supplement HVTN’s work by conducting its own investigation into the dynamics of immune responses, as well as conducting additional assay to better assess the breadth and potency of antibodies elicited by the PDPHV vaccine candidate. WHV formally applied to HVTN to request the samples from volunteers needed for the study and the request has been approved.
This work will be conducted in collaboration with Dr. Shan Lu’s Laboratory of Nucleic Acid Vaccines (LNAV) at the UMMS in Worcester, MA. Dr. Lu is the co-inventor of the PDPHV vaccine candidate and his laboratory has extensive expertise in assessing immune responses to the DNA/protein vaccines. Another co-inventor, Dr. Shixia Wang, will lead the studies. The results from both the HVTN study and the exploratory study by WHV will be available later this year.
