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The Weiner Lab

David B. Weiner, Ph.D.

Laboratory

The Weiner Laboratory

Contact

215-898-0381
jhubert@wistar.org

Executive Vice President

Director, Vaccine & Immunotherapy Center

W.W. Smith Charitable Trust Professor in Cancer Research

Professor, Immunology, Microenvironment & Metastasis Program

About the Scientist

Professor Emeritus at the University of Pennsylvania School of Medicine.

Weiner directs a translational molecular immunology research team focused on creating novel immunotherapy approaches for disease prevention and treatment using synthetic nucleic acid technology. Accomplishments of the team and collaborators include the first clinical studies of DNA vaccines, with a focus on advances in gene optimization and electroporation (EP)-mediated DNA delivery. Their work has revitalized the field, rapidly and safely moving new advances into human studies. These include the world’s first Zika vaccine, the first MERS vaccine, an advanced Ebola Vaccine, and a novel HIV vaccine, among others. Additionally, the Weiner laboratory has helped to develop immunotherapy approaches that are currently in clinical testing for HPV-associated cancer, prostate and other cancers. The first clinically efficacious therapeutic DNA vaccine for HPV cervical intraepithelial neoplasia CIN) has moved into a licensure trial (REVEAL). Weiner and his lab have received several awards/honors for their accomplishments, including the Vaccine Industry Associations Outstanding Academic Research Laboratory (2015 & 2016), being named one of the Top 20 Translational Research Laboratories of the Year (Nature Biotechnology 2016, 2017 &  2018) and the 2014 Stone family Award for Cancer Research. Weiner was named one of the nation’s top 40 most influential vaccine scientists in 2014, received the 2011 NIH Directors Translational Research Award and is an elected fellow of the American Association for the Advancement of Science since 2011 and a fellow of the International Society for Vaccines, for which he served as president from 2018 to 2020. Weiner is an avid trainer, advisor and advocate for students, fellows and junior faculty as he is highly committed to developing the careers of young scientists.  

Weiner received his B.S. in biology from Stony Brook University, N.Y., and his M.S. in biology from the University of Cincinnati. He then earned a Ph.D. in developmental biology with a focus on molecular immunology from the University of Cincinnati, College of Medicine. Weiner joined the University of Pennsylvania as a research fellow in the Department of Pathology and Laboratory Medicine, where he rose through the ranks to become Professor. He held a second appointment from The Wistar Institute from 1990 to 1993. At Penn, he served as co-chair of the Tumor Virology Program of the Abramson Cancer Institute and as chair of the Gene Therapy and Vaccine Training Program.

View Publications

The Weiner Laboratory

The Weiner laboratory represents one of the pioneering research teams in the field of DNA vaccines and immunotherapies. The lab has published more than 420 scientific papers, chapters and reviews, including many seminal papers in the DNA vaccine and synthetic nucleic acids field, and is credited with generating more than 70 patents. Along with collaborators, the Weiner Lab was the first to move DNA vaccines to human clinical studies, establishing their initial safety and immunogenicity. The team also helped to develop the new field of nucleic zcid-encoded antibodies, or dMAbs. More than a dozen experimental clinical therapies and vaccines have been developed from research from the Weiner laboratory, including the first Zika vaccine in clinical trials, the first MERS vaccine, a novel Ebola vaccine as well as novel immunotherapy for HPV-associated cancer and precancer, and a novel immunotherapeutic vaccine for glioblastoma. Other notable reports from the Weiner lab include the first DNA vaccine studied for HIV and for immunotherapy of cutaneous T-cell lymphoma and the early development of DNA-encoded genetic adjuvants, including IL-12.Program.

Staff

Staff Scientist

Makan Khoshnejad, Ph.D.

Research Assistant Professor

Ami Patel, Ph.D.

Postdoctoral Fellows

Elizabeth Parzych, Ph.D.
Emma Reuschel, Ph.D.

Predoctoral Trainees

Pratik Bhojngarwala
Lumena Louis
Sophia Reeder
Krzysztof Wojtak
Ziyang Xu
Michael Zhu

Research Assistants

Mamadou Bah
Jacqueline Chu
Kevin Kim
Edgar Tello Ruiz
Regina Stoltz

Project Manager

Faraz Zaidi

Program Manager

Michael Merva

Lab Coordinator

Jeneice Hubert

Research

Bill and Melinda Gates Project

The Zika virus has become a global health concern due to its rapid spread and concerning link to microcephaly in infants. The Weiner lab has received funding from the Bill and Melinda Gates foundation for a collaborative project with Inovio Pharmaceuticals and HUMABS BioMed to develop DNA encoded monoclonal antibodies (DMAbs) against Zika. DMAbs are injected into the muscle and the human body is used as its own bioreactor to produce protective antibodies. Working with highly effective antibodies for which sequences were provided by HUMABS, the Weiner lab is optimizing DMAbs for high levels of expression, binding, and neutralization. Once these DMAbs are shown to be protective in mice, they will be tested in nonhuman primates and eventually prepared for clinical trials with the assistance of Inovio.

Ebola

Ebola virus causes the highly lethal Ebola virus disease (EVD), characterized by a severe hemorrhagic fever and a mortality rate ranging from 50 to 90 percent. The virus was first identified in 1976 and has been responsible for isolated outbreaks. The 2013-2016 EVD outbreak in West Africa was the largest to-date, with more than 28,500 confirmed cases and over 11,000 deaths. This was the first time that cases were confirmed in countries outside of Africa, highlighting concerns that global travel could increase spread of the virus to new populations. There are currently no approved preventative or post-exposure vaccines or therapeutics available for EVD treatment. The Ebola virus is classified as a Category "A" Priority Pathogen by the U.S. Centers for Disease Control and Prevention.

The Weiner lab is a key member of a $45 million collaborative grant from the U.S. Defense Advanced Research Projects Agency (DARPA). This grant is led by Inovio Pharmaceuticals with the goal of utilizing the DNA platform to develop a multi-faceted approach against Ebola virus infection. The Wistar team is involved in the development of DNA-based vaccines against EVD and a DNA-based monoclonal antibody (DMAb) to treat EVD. Other partners on this grant include MedImmune, the Public Health Agency of Canada, and Université Laval.

The team has developed an EVD DNA vaccine that is 100 percent protective in cynomolgus macaques against lethal Ebola virus challenge. This vaccine has entered a Phase I clinical trial (clinicaltrials.gov: NCT02464670).

The team is also working on prevention of related Ebolavirus members Sudan virus (SUDV) and Bundibugyo virus (BDBV), and the related filovirus Marburg virus.

Integrated Preclinical/ Clinical AIDS Vaccine Development Program

The Weiner lab has a long history of working on DNA vaccine for human immunodeficiency virus (HIV). The lab is currently a part of a multi-institutional group working on developing a prophylactic HIV vaccine under a five year Integrated Preclinical/Clinical AIDS Vaccine Development Program grant from the National Institutes of Allergy and Infectious Disease (NIAID). Working with Inovio Pharmaceuticals, Duke University, Emory University, University of Massachusetts and the National Institutes of Health, the group aims to build on the success of previous generations of DNA vaccines in order to induce strong cellular and humoral responses. The main focus of the program is inducing broad responses against the diverse HIV surface protein, Env.

Basser Center for BRCA Project

The Weiner lab has teamed up with investigators at the University of Pennsylvania to develop a novel vaccine to prevent cancer development in high-risk patient populations. This includes individuals who carry mutations in the BRCA1 or BRCA2 genes and are susceptible to the development of breast, pancreatic and ovarian cancer. This novel vaccine encodes the tumor antigen TERT, which is highly expressed in tumor cells, and is particularly high in tumor samples from patients with mutations in DNA damage repair pathways, such as the BRCA1/BRCA2 pathway. The lab developed this vaccine and is currently working to improve the efficacy of the vaccine using combination therapies with immune checkpoint blockade antibodies in mouse models. In parallel, a clinical trial is being conducted for high-risk patients in remission after adjuvant therapy for TERT DNA vaccine with or without IL-12 immune plasmid adjuvant. This project is funded by a Breakthrough Science Team Award through the Basser Research Center for BRCA at the University of Pennsylvania.

Penn/Inovio/MedImmune (PIM) Project

The Weiner lab has formed a collaboration with Inovio Pharmaceuticals and MedImmune to develop DNA-encoded monoclonal antibody (DMAb) against Influenza virus and emerging antibiotic-resistant bacteria, including Pseudomonas aeruginosa and Staphylococcus aureus. This program is funded by the Defense Advanced Research Projects Agency (DARPA). Highly-engineered monoclonal antibody sequences are encoded in a DNA plasmid and delivered directly into cells of the body using electroporation, resulting in protective monoclonal antibodies "manufactured" in the body – versus recombinant proteins manufactured and purified in vitro. Given the scalability of DNA manufacturing and ease of DNA delivery relative to conventional recombinant protein monoclonal antibody therapies, the DMAb platform has potential to greatly expand the market for monoclonal antibody prophylaxis/therapy against challenging infectious disease targets.

Selected Publications

Duperret, E.K., Trautz, A., Weiner D.B., et al. "Alteration of the Tumor Stroma Using a Consensus DNA Vaccine Targeting Fibroblast Activation Protein (FAP) Synergizes with Antitumor Vaccine Therapy in Mice." Clin Cancer Res. 2018 Mar 1;24(5):1190-1201. doi: 10.1158/1078-0432.CCR-17-2033. Epub 2017 Dec 21.

Tebas, P., Roberts, C.C., Muthumani, K., Reuschel, E.L., Kudchodkar, S.B., Zaidi, F.I., White, S., Khan, A.S., Racine, T., Choi, H., Boyer, J., Park, Y.K., Trottier, S., Remigio, C., Krieger, D., Spruill, S.E., Bagarazzi, M., Kobinger, G.P., Weiner, D.B., Maslow, J.N. "Safety and Immunogenicity of an Anti-Zika Virus DNA Vaccine - Preliminary Report." N Engl J Med. 2017 Oct 4. doi: 10.1056/NEJMoa1708120. [Epub ahead of print]

Patel, A., DiGiandomenico, A., Weiner, D.B., et al. "An engineered bispecific DNA-encoded IgG antibody protects against Pseudomonas aeruginosa in a pneumonia challenge model." Nat Commun. 2017 Sep 21;8(1):637. doi: 10.1038/s41467-017-00576-7.

Elliott, S.T.C., Kallewaard, N.L., Weiner, D.B., et al. "DMAb inoculation of synthetic cross reactive antibodies protects against lethal influenza A and B infections." NPJ Vaccines. 2017 Jul 6;2:18. doi: 10.1038/s41541-017-0020-x. eCollection 2017.

Trimble, C.L., Morrow, M.P., Kraynyak, K.A., Shen, X., Dallas, M., Yan, J., Edwards, L., Parker, R.L., Denny, L., Giffear, M., Brown, A.S., Marcozzi-Pierce, K., Shah, D., Slager, A.M., Sylvester, A.J., Khan, A., Broderick, K.E., Juba, R.J., Herring, T.A., Boyer, J., Lee, J., Sardesai, N.Y., Weiner, D.B., Bagarazzi, M.L. "Safety, efficacy, and immunogenicity of VGX-3100, a therapeutic synthetic DNA vaccine targeting human papillomavirus 16 and 18 E6 and E7 proteins for cervical intraepithelial neoplasia 2/3: a randomised, double-blind, placebo-controlled phase 2b trial." Lancet. 2015 Nov 21;386(10008):2078-2088. doi: 10.1016/S0140-6736(15)00239-1. Epub 2015 Sep 17.

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