Oncolytic recombinant vesicular stomatitis virus (VSV) is nonpathogenic and non-transmissible in pigs, a natural host of VSV

Authors: VELAZQUEZ-SALINAS, LAURO - Oak Ridge Institute For Science And Education (ORISE); NIAK, SHRUTHI - Mayo Clinic College Of Medicine; PENG, KAH WHYE - Mayo Clinic College Of Medicine; Pauszek, Steven; Rodriguez, Luis

Submitted to: Human Gene Therapy
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/12/2017
Publication Date: 5/17/2017
Citation: Velazquez-Salinas, L., Niak, S., Peng, K., Pauszek, S.J., Rodriguez, L.L. 2017. Oncolytic recombinant vesicular stomatitis virus (VSV) is nonpathogenic and non-transmissible in pigs, a natural host of VSV. Human Gene Therapy. 28(2):108-115.

Interpretive Summary: Vesicular stomatitis (VS) is a disease of agricultural livestock including horses, cattle and pigs. VS is caused by a virus (VSV) that is transmitted by biting midges and flies. VSV has been extensively studied since it grows very well in laboratory conditions. In addition to causing animal disease, VSV has neem recently shown to be very useful as a method to deliver vaccines to humans such as the most effective Ebola vaccine (EBOVSV) and also as a novel method to treat cancer. The cancer treatment is based on VSV that have been engineered in the laboratory to be harmless to humans and animals but still retain the capacity to target and destroy cancer cells (i.e. oncolytic therapy). Scientists from the Mayo Clinic and from Vyriad Inc. both in Rochester MN, developed a VSV (VSV-IFNß-NIS) that has been tested in cancer treatment in humans and also in dogs. Although this virus has been shown to be safe in humans and dogs, there was a need to show that was also safe to farm animals that might come accidently in contact with the virus. ARS researchers at the Plum Island Animal disease Center in Orient NY, collaborated with their MN colleagues to support clinical studies and comprehensively assess the risk of transmission and disease in susceptible species of oncolytic VSV-IFNß-NIS using the swine model ARS had previously developed. Following previously established protocols to evaluate VSV pathogenicity, intradermal inoculation of VSV-IFNß-NIS did not cause disease in pigs. Further, there was no detectable shedding of VSV-IFNß-NIS in biological excreta of inoculated or contact pigs. These data indicate that oncolytic VSV is both non-pathogenic and not transmissible in pigs, a natural host. These findings support further clinical development of oncolytic VSV-IFNß-NIS as a safe therapeutic for human and canine cancer. The study also illustrates the contribution of ARS to improving human health and well-being through cutting edge research and meaningful collaborations.

Technical Abstract: Vesicular stomatitis virus (VSV) is a negative stranded RNA virus that naturally causes disease in agricultural livestock including horses, cattle and pigs. The two main identified VSV strains are the New Jersey (VSNJV) and Indiana (VSIV) strains. 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, and has been utilized to determine pathogenicity and transmissibility of wild-type isolates and recombinant VSIV and VSNJV. Oncolytic VSV engineered to express Interferon-beta (IFNß) and the sodium iodide symporter (NIS), VSV-IFNß-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-IFNß-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-IFNß- NIS using the swine model. Following previously established protocols to evaluate VSV pathogenicity, intradermal inoculation with 107 TCID50 VSV-IFNß-NIS caused no observable symptoms in pigs. This was in contrast to pigs that developed lesions, including snout and secondary foot lesion following exposure to wild type VSIV and VSNJV isolates. There was no detectable shedding of infectious virus in VSV-IFNß-NIS in biological excreta of inoculated or contact pigs. VSV-IFNß-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 non-pathogenic and not transmissible in pigs, a natural host. These findings support further clinical development of oncolytic VSV-IFNß-NIS as a safe therapeutic for human and canine cancer.