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| vaccines | |
NS1 Attenuated VaccinesUsing reverse genetics, we are studying attenuated influenza viruses containing defined mutations in the NS1 interferon-antagonist protein that might prove to be optimal live vaccines against influenza. We are conducting pre-clinical and veterinary studies of vaccine protection and immune induction in animal models, including mice and livestock. The generation and evaluation of influenza virus vectors as potential vaccine candidates against different infectious diseases, including malaria and HIV (the causative virus in AIDS), is also underway in collaboration with the Center for Investigating Viral Immunity and Antagonism (CIVIA). Development of HIV Vaccines Using Newcastle Disease Virus (NDV) Vectors Newcastle Disease virus (NDV) is an avian virus that is not pathogenic in humans. As such, it is proposed as a safe vaccine vector, which has the additional advantage that there is no pre-existing immunity in the human population. Using reverse genetics, we are constructing recombinant NDV carrying HIV Gag as an immunogen. Our goal is the optimization of expression of HIV Gag antigen by NDV in order to induce a protective immune response. Oncolytic Therapy for Cancer Using Genetically-Modified Newcastle Disease Virus (NDV) Naturally occurring strains of Newcastle disease virus (NDV) have the ability to target tumor cells. The efficacy of NDV as an oncolytic therapeutic is underway in preclinical studies and clinical trials. We are enhancing the cancer therapeutic potential of NDV by reverse genetics. A recombinant NDV modified to contain a highly fusogenic F protein significantly reduces growth and metastasis of an implanted colon carcinoma in mice, in comparison to an unmodified virus. Furthermore, the oncolytic properties of NDV could be improved by expression of immunostimulatory molecules such as IL-2. We are now studying the potential of enhanced recombinant NDV vectors as effective therapeutic agents for cancer treatment in human patients. A. VIGIL, M.-S. PARK, O. MARTINEZ, M.A. CHUA, S. XIAO, J.F. CROS, L. MARTÍNEZ-SOBRIDO, S.L.C. WOO & A. GARCÍA-SASTRE: Use of reverse genetics to enhance the oncolytic properties of Newcastle disease virus. Cancer Research, 67, 8285-8292 (2007). L. MARTÍNEZ-SOBRIDO & A. GARCÍA-SASTRE: Recombinant influenza virus vectors. Future Virology, 2, 401-416 (2007). J.A. RICHT, P. LEKCHAROENSUK, K.M. LAGER, A.L. VINCENT, C.M. LOIACONO, B.H. JANKE, W.-H. WU, K.-J. YOON, R.J. WEBBY, A. SOLÓRZANO & A. GARCÍA-SASTRE: Vaccination of pigs against swine influenza viruses using an NS1-truncated modified live virus vaccine. Journal of Virology, 80, 11009-11018 (2006). P. PALESE & A. GARCÍA-SASTRE: Influenza vaccines: present and future. The Journal of Clinical Investigation, 110, 9-13 (2002). |
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| Copyright © 2007, Mount Sinai School of Medicine |
