As cancer treatment tools, oncolytic viruses (OV) have yet to realize what some see as their ultimate clinical potential. In this study, we have engineered a chimeric vesicular stomatitis virus (VSV) that is devoid of its natural neurotoxicity while retaining potent oncolytic activity. The envelope glycoprotein (G) of VSV was replaced with a variant glycoprotein of the lymphocytic choriomeningitis virus (LCMV-GP), creating a replicating therapeutic, rVSV (GP), that is benign in normal brain but can effectively eliminate brain cancer in multiple preclinical tumor models in vivo. Furthermore, it can be safely administered systemically to mice and displays greater potency against a spectrum of human cancer cell lines than current OV candidates. Remarkably, rVSV(GP) escapes humoral immunity, thus, for the first time, allowing repeated systemic OV application without loss of therapeutic efficacy. Taken together, rVSV(GP) offers a considerably improved OV platform that lacks several of the major drawbacks that have limited the clinical potential of this technology to date. Cancer Res; 74(13); 3567-78. Ó2014 AACR.

Antivector immunity limits the response to homologous boosting for viral vector vaccines. Here, we describe a new, potent vaccine vector based on replication-competent vesicular stomatitis virus pseudotyped with the glycoprotein of the lymphocytic choriomeningitis virus (VSV-GP), which we previously showed to be safe in mice. In mice, VSV and VSV-GP encoding ovalbumin (OVA) as a model antigen (VSV-OVA and VSV-GP-OVA) induced equal levels of OVA-specific humoral and cellular immune responses upon a single immunization. However, boosting with the same vector was possible only for VSV-GP-OVA as neutralizing antibodies to VSV limited the immunogenicity of the VSV-OVA boost. OVA-specific cytotoxic T-lymphocyte (CTL) responses induced by VSV-GP-OVA were at least as potent as those induced by an adenoviral state-of-the-art vaccine vector and completely protected mice in a Listeria monocytogenes challenge model. VSV-GP is so far the only replication-competent vaccine vector that does not lose efficacy upon repeated application. IMPORTANCE Although there has been great progress in treatment and prevention of infectious diseases in the past

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Bovine papillomavirus types 1 and 2 (BPV-1 and BPV-2) are known to induce common equine skin tumours, termed sarcoids. Recently, it was demonstrated that vaccination with BPV-1 viruslike particles (VLPs) is safe and highly immunogenic in horses. To establish a BPV-1 challenge model for evaluation of the protective potential of BPV-1 VLPs, four foals were injected intradermally with infectious BPV-1 virions and with viral genome-based and control inocula, and monitored daily for tumour development. Blood was taken before inoculation and at weekly intervals. BPV-1-specific serum antibodies were detected by a pseudo-virion neutralization assay. Total nucleic acids extracted from tumours, intact skin and PBMCs were tested for the presence of BPV-1 DNA and mRNA using PCR and RT-PCR, respectively. Intralesional E5 oncoprotein expression was determined by immunofluorescence. Pseudo-sarcoids developed exclusively at sites inoculated with virions. Tumours became palpable 11-32 days after virion challenge, reached a size of ≤20 mm in diameter and then resolved in ≤6 months. No neutralizing anti-BPV-1 serum antibodies were detectable pre-or post-challenge. BPV-1 DNA was present in lesions but not in intact skin. In PBMCs, viral DNA was already detectable before lesions were first palpable, in concentrations correlating directly with tumour growth kinetics. PBMCs from two of two foals also harboured E5 mRNA. Immunofluorescence revealed the presence of the E5 protein in tumour Correspondence Sabine Brandt sabine.brandt@vetmeduni.ac.at.

The use of antivirals and/or immune modulators may help improving canker therapy.