TY - JOUR
T1 - Oncolytic Recombinant Vesicular Stomatitis Virus (VSV) Is Nonpathogenic and Nontransmissible in Pigs, a Natural Host of VSV
AU - Velazquez-Salinas, Lauro
AU - Naik, Shruthi
AU - Pauszek, Steven J.
AU - Peng, Kah Whye
AU - Russell, Stephen J.
AU - Rodriguez, Luis L.
N1 - Publisher Copyright:
© 2017, Mary Ann Liebert, Inc.
PY - 2017/6
Y1 - 2017/6
N2 - Vesicular stomatitis virus (VSV) is a negative-stranded RNA virus that naturally causes disease in livestock including horses, cattle and pigs. The two main identified VSV serotypes are New Jersey (VSNJV) and Indiana (VSIV). VSV is a rapidly replicating, potently immunogenic virus that has been engineered to develop novel oncolytic therapies for cancer treatment. Swine are a natural host for VSV and provide a relevant and well-established model, amenable to biological sampling to monitor virus shedding and neutralizing antibodies. Previous reports have documented the pathogenicity and transmissibility of wild-type isolates and recombinant strains of VSIV and VSNJV using the swine model. Oncolytic VSV engineered to express interferon-beta (IFNβ) and the sodium iodide symporter (NIS), VSV-IFNβ-NIS, has been shown to be a potent new therapeutic agent inducing rapid and durable tumor remission following systemic therapy in preclinical mouse models. VSV-IFNβ-NIS is currently undergoing clinical evaluation for the treatment of advanced cancer in human and canine patients. To support clinical studies and comprehensively assess the risk of transmission to susceptible species, we tested the pathogenicity and transmissibility of oncolytic VSV-IFNβ-NIS using the swine model. Following previously established protocols to evaluate VSV pathogenicity, intradermal inoculation with 107 TCID50 VSV-IFNβ-NIS caused no observable symptoms in pigs. There was no detectable shedding of infectious virus in VSV-IFNβ-NIS in biological excreta of inoculated pigs or exposed naive pigs kept in direct contact throughout the experiment. VSV-IFNβ-NIS inoculated pigs became seropositive for VSV antibodies, while contact pigs displayed no symptoms of VSV infection, and importantly did not seroconvert. These data indicate that oncolytic VSV is both nonpathogenic and not transmissible in pigs, a natural host. These findings support further clinical development of oncolytic VSV-IFNβ-NIS as a safe therapeutic for human and canine cancer.
AB - Vesicular stomatitis virus (VSV) is a negative-stranded RNA virus that naturally causes disease in livestock including horses, cattle and pigs. The two main identified VSV serotypes are New Jersey (VSNJV) and Indiana (VSIV). VSV is a rapidly replicating, potently immunogenic virus that has been engineered to develop novel oncolytic therapies for cancer treatment. Swine are a natural host for VSV and provide a relevant and well-established model, amenable to biological sampling to monitor virus shedding and neutralizing antibodies. Previous reports have documented the pathogenicity and transmissibility of wild-type isolates and recombinant strains of VSIV and VSNJV using the swine model. Oncolytic VSV engineered to express interferon-beta (IFNβ) and the sodium iodide symporter (NIS), VSV-IFNβ-NIS, has been shown to be a potent new therapeutic agent inducing rapid and durable tumor remission following systemic therapy in preclinical mouse models. VSV-IFNβ-NIS is currently undergoing clinical evaluation for the treatment of advanced cancer in human and canine patients. To support clinical studies and comprehensively assess the risk of transmission to susceptible species, we tested the pathogenicity and transmissibility of oncolytic VSV-IFNβ-NIS using the swine model. Following previously established protocols to evaluate VSV pathogenicity, intradermal inoculation with 107 TCID50 VSV-IFNβ-NIS caused no observable symptoms in pigs. There was no detectable shedding of infectious virus in VSV-IFNβ-NIS in biological excreta of inoculated pigs or exposed naive pigs kept in direct contact throughout the experiment. VSV-IFNβ-NIS inoculated pigs became seropositive for VSV antibodies, while contact pigs displayed no symptoms of VSV infection, and importantly did not seroconvert. These data indicate that oncolytic VSV is both nonpathogenic and not transmissible in pigs, a natural host. These findings support further clinical development of oncolytic VSV-IFNβ-NIS as a safe therapeutic for human and canine cancer.
KW - Oncolytic virus
KW - biosafety
KW - pig model
KW - vesicular stomatitis virus
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U2 - 10.1089/humc.2017.015
DO - 10.1089/humc.2017.015
M3 - Article
C2 - 28514874
AN - SCOPUS:85020805999
SN - 2324-8637
VL - 28
SP - 108
EP - 115
JO - Human Gene Therapy Clinical Development
JF - Human Gene Therapy Clinical Development
IS - 2
ER -