Lab In The News
A Look at Inovio’s Philly Local Coronavirus Vaccine-in-Progress
Operation Warp Speed, the federal government’s multi-agency push to develop a COVID-19 vaccine, is promising to provide 300 million doses by January 2021. That means funding for several of the top candidates.
Low-dose Administration of MERS DNA Vaccine Candidate Induces Potent Immunity and Protects From Virus Challenge in Preclinical ModelsDose-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 Patel Laboratory
The Patel laboratory focuses on vaccine and immunotherapy development against emerging infectious diseases, including study of immune mechanisms that contribute to protection from pathogens. Research in the lab employs non-viral DNA vectors for vaccine and antibody delivery. Patel’s most recent studies include DNA vaccine development against Ebola virus, Middle East respiratory syndrome coronavirus (MERS-CoV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and multiple studies in the rapidly advancing field of DNA-encoded monoclonal antibodies (DMAbs). Her preclinical animal studies have led to the successful clinical translation of anti-Ebola virus GP DNA vaccine and anti-Zika virus DMAb candidates (NCT03831503). Patel is part of a team at the Wistar Vaccine & Immunotherapy Center leading preclinical immunological studies of a SARS-CoV-2/COVID-19 DNA vaccine candidate. This vaccine candidate entered the clinic in about 10 weeks from vaccine design to FDA approval and trial initiation (NCT04336410 and NCT04447781).
DNA VACCINE DEVELOPMENT AGAINST EMERGING INFECTIOUS DISEASES
Patel’s most recent studies include DNA vaccine development against Ebola virus, Middle East respiratory syndrome coronavirus (MERS-CoV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19 disease. Emerging respiratory pathogens including influenza A/B viruses and seasonal coronaviruses, as well as antimicrobial-resistant bacteria are also of interest. In addition to vaccine development, the lab studies potential correlates of protection (antibodies and T cells) in non-human primate samples to improve vaccine development and efficacy and bridge results from animal studies with human clinical data.
DNA-ENCODED MONOCLONAL ANTIBODY (DMAB) DELIVERY AGAINST INFECTIOUS DISEASES
Nucleic acid gene-encoded antibodies are a rapidly advancing field. Patel’s preclinical animal studies have led to the successful clinical translation of an anti-Zika virus DMAb candidate (NCT03831503). The lab’s research interests include approaches to improve DMAb protective efficacy through sequence engineering and strategies for effector function/immune cell recruitment. This includes understanding ways to modulate the early innate immune responses against DNA vectors to improve long-term duration in vivo. These studies could have interesting implications for both infectious diseases antibody delivery as well as different gene therapy approaches.
Smith ,T.R.F.*, Patel, A.*, Ramos, S.*, Elwood, D., Zhu, X., Yan, J., Gary, E.N., Walker, S.N., Schultheis, K., Purwar, M., Xu, Z., Walters, J., Bhojnagarwala, P., Yang, M., Chokkalingam, N., Pezzoli, P., Parzych, E., Reuschel, E.L., Doan, A., Tursi, N., Vasquez, M., Choi, J., Tello-Ruiz, E., Maricic, I., Bah, M.A., Wu, Y., Amante, D., Park, D.H., Dia, Y., Ali, A.R., Zaidi, F.I., Generotti, A., Kim, K.Y., Herring, T.A., Reeder, S., Andrade, V.M., Buttigieg, K., Zhao, G., Wu, J.M., Li, D., Bao, L., Liu, J., Deng, W., Qin, C., Brown, A.S., Khoshnejad, M., Wang, N., Chu, J., Wrapp, D., McLellan, J.S., Muthumani, K., Wang, B., Carroll, M.W., Kim, J.J., Boyer, J., Kulp, D.W., Humeau, L., Weiner, D.B., Broderick, K.E. “Immunogenicity of a DNA vaccine candidate for COVID-19.” Nat Commun. 2020;11(1):2601. Epub 2020/05/21. doi: 10.1038/s41467-020-16505-0. PubMed PMID: 32433465.
Tebas, P., Kraynyak, K.A., Patel, A., Maslow, J.N., Morrow, M.P., Sylvester, A.J., Knoblock, D., Gillespie, E., Amante, D., Racine, T., McMullan, T., Jeong, M., Roberts, C.C., Park, Y.K., Boyer, J., Broderick, K.E., Kobinger, G.P., Bagarazzi, M., Weiner, D.B., Sardesai, N.Y., White, S.M. “Intradermal SynCon(R) Ebola GP DNA Vaccine Is Temperature Stable and Safely Demonstrates Cellular and Humoral Immunogenicity Advantages in Healthy Volunteers.” J Infect Dis. 2019;220(3):400-10. Epub 2019/03/21. doi: 10.1093/infdis/jiz132. PubMed PMID: 30891607.
Patel, A., Reuschel, E.L., Kraynyak, K.A., Racine, T., Park, D.H., Scott, V.L., Audet, J., Amante, D., Wise, M.C., Keaton, A.A., Wong, G., Villarreal, D.O., Walters, J., Muthumani, K., Shedlock, D.J., de La Vega, M.A., Plyler, R., Boyer, J., Broderick, K.E., Yan, J., Khan, A.S., Jones, S., Bello, A., Soule, G., Tran, K.N., He, S., Tierney, K., Qiu, X., Kobinger, G.P., Sardesai, N.Y., Weiner, D.B. “Protective Efficacy and Long-Term Immunogenicity in Cynomolgus Macaques by Ebola Virus Glycoprotein Synthetic DNA Vaccines.” J Infect Dis. 2019;219(4):544-55. Epub 2018/10/12. doi: 10.1093/infdis/jiy537. PubMed PMID: 30304515.
Esquivel, R.N.*, Patel, A.*, Kudchodkar, S.B., Park, D.H., Stettler, K., Beltramello, M., Allen, J.W., Mendoza, J., Ramos, S., Choi, H., Borole, P., Asija, K., Bah, M., Shaheen, S., Chen, J., Yan, J., Durham, A.C., Smith, T.R.F., Broderick, K., Guibinga, G., Muthumani, K., Corti, D., Humeau, L., Weiner, D.B. “In Vivo Delivery of a DNA-Encoded Monoclonal Antibody Protects Non-human Primates against Zika Virus.” Mol Ther. 2019;27(5):974-85. Epub 2019/04/10. doi: 10.1016/j.ymthe.2019.03.005. PubMed PMID: 30962164; PMCID: PMC6520333.
Patel, A., Park, D.H., Davis, C.W., Smith, T.R.F., Leung, A., Tierney, K., Bryan, A., Davidson, E., Yu, X., Racine, T., Reed, C., Gorman, M.E., Wise, M.C., Elliott, S.T.C., Esquivel, R., Yan, J., Chen, J., Muthumani, K., Doranz, B.J., Saphire, E.O., Crowe, J.E., Broderick, K.E., Kobinger, G.P., He, S., Qiu, X., Kobasa, D., Humeau, L., Sardesai, N.Y., Ahmed, R., Weiner, D.B. “In Vivo Delivery of Synthetic Human DNA-Encoded Monoclonal Antibodies Protect against Ebolavirus Infection in a Mouse Model.” Cell Rep. 2018;25(7):1982-93 e4. Epub 2018/11/15. doi: 10.1016/j.celrep.2018.10.062. PubMed PMID: 30428362; PMCID: PMC6319964.
Kazuko Nishikura, Ph.D.
Professor, Gene Expression & Regulation Program, Ellen and Ronald Caplan Cancer Center