Lab In The News
Positive Results from Preclinical Testing Support Clinical Development of COVID-19 DNA Vaccine
PHILADELPHIA — (May 20, 2020) — The Wistar Institute, an international biomedical research leader in cancer, immunology and infectious disease, announces a study reporting initial immunogenicity of a synthetic DNA vaccine for SARS-CoV-2 developed in collaboration with Inovio Phar
Low-dose Administration of MERS DNA Vaccine Candidate Induces Potent Immunity and Protects From Virus Challenge in Preclinical Models
Dose-sparing regimens and intradermal delivery have important implication for rapid clinical development of effective, well-tolerated and easy-to-distribute vaccines against MERS and other emerging coronaviruses.
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.
Emma Reuschel, Ph.D.
Devivasha Bordoloi, Ph.D.
Ebony N. Gary, Ph.D.
Kevin Liaw, Ph.D.
Elizabeth Parzych, Ph.D.
Mansi Purwar, Ph.D.
Ali Raza Ali
Current Projects and Funding Sources
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 & 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.
DNA VACCINE & DMAb CO-DELIVERY FOR VACCINAL EFFECT
Funded by the Bill & Melinda Gates Foundation, this study addresses the possibility of achieving vaccinal effect by co-delivering DNA-encoded monoclonal antibodies (DMAbs) and synthetic DNA vaccines to prevent HIV infection.
Funded by the Bill & Melinda Gates Foundation, the focus of this study is to develop new synthetic DNA vaccines encoding designed circumsporozoite protein (CSP) antigens to provide a new generation advanced CSP component for a prophylactic malaria vaccine.
INTEGRATED PRECLINICAL CLINICAL HIV 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.
VACCINE FOR BRCA-RELATED CANCERS
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 efficacy 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.
Funded by the Department of Defense (DoD), this study will characterize a novel vaccine targeting follicle stimulating hormone receptor (FSHR) in ovarian cancer.
COLLABORATIVE INFLUENZA VACCINE INNOVATION CENTERS (CIVICS) PROGRAM
The objective of this study is to support improvements in the immunogenicity and durability of seasonal influenza vaccines, and the development of innovative influenza vaccine approaches that provide robust, durable, broadly protective mucosal and systemic anti-influenza immunity (“universal influenza vaccines”). Research Area 003 will support iterative vaccine design based on detailed immunologic assessment of influenza vaccine candidates through preclinical animal studies, early phase clinical trials and healthy volunteer human challenge studies, to advance the most promising vaccine candidates into phase 1/2 clinical trials.
LASSA VIRUS AND MERS CORONAVIRUS
Translational Platform Program encompassing cGMP manufacturing and clinical development of DNA vaccine candidates against both Lassa virus and MERS coronavirus, with funding from the Coalition for Epidemic Preparedness Innovations (CEPI).
NOVEL CORONAVIRUS COVID-19 EMERGENCY SUPPLEMENT
Funded by the Coalition for Epidemic Preparedness Innovations (CEPI), Wistar will support the development of a synthetic DNA vaccine and nanoparticles against Wuhan coronavirus 2019-nCoV. Successful characterization of the blocking antibody will permit us to explore monoclonal antibody production, engineer the monoclonal antibody into the synthetic DNA-based DMAb platform, and engineer into the nanoparticle platform as potential vaccines and immunotherapeutics against the Wuhan Coronavirus 2019-nCoV.
This NIH-funded study addresses Novel DNA-encoded monoclonal antibodies (DMAbs) for control of antimicrobial tesistant (AMR) Pseudomonas aeruginosa infection.
This NIH-funded study addresses development of a multivalent, DNA vaccine-mediated protection against Tuberculosis.
Duperret, E.K., Trautz, A., Ammons, D., Perales-Puchalt, A., Wise, M.C., Yan, J., Reed, C., Weiner, D.B. "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., et al. "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., Keller, A.E., Smith, T.R.F., Park, D.H., Ramos, S., Schultheis, K., Elliott, S.T.C., Mendoza, J., Broderick, K.E., 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., Benjamin, E., Wachter-Rosati, L., McAuliffe, J.M., Patel, A., Smith, T.R.F., Schultheis, K., Park, D.H., Flingai, S., 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., et al. "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.
Jessie Villanueva, Ph.D.
Associate Professor, Molecular & Cellular Oncogenesis Program, The Wistar Institute Cancer Center
Member, The Wistar Institute Melanoma Research Center
Scientific Director, Animal Facility