Prophylaktisches Potential einer anti-BPV-1/-2 Vakzine im Pferd

Projektleitung an der Vetmeduni

Brandt, Sabine

Geldgeber

FWF Österreichischer Wissenschaftsfonds

Laufzeit

01.07.2011 - 31.12.2015

Abstract

Equine sarcoids are persistent, locally aggressive skin tumours induced by bovine papillomaviruses of types 1 and 2 (BPV-1, BPV-2). Given that no prophylactic vaccine is so far available, this common disease constitutes a significant veterinary problem. Papillomavirus (PV)-like particles (VLPs) have been shown to be well tolerated and effective vaccines against PV infection-mediated tumour formation in several species. A VLP-based vaccine for prevention of human PV (HPV)-induced cervical cancer in women has been recently introduced on the market.We have shown that immunisation of horses with BPV-1 L1 VLPs has minimal side effects and results in high titres of type-specific neutralising antibodies. We could also demonstrate that BPV-1 and BPV-2 are sero-analogues. We hence postulate that vaccination with BPV-1 VLPs can avert infection by BPV-1 and -2 and thus prevent equine sarcoid development.To be able to address this assumption, we then established a virus challenge model. Four weanling foals were intradermally inoculated with BPV-1 virion, equine fibroblasts harbouring BPV-1 episomes and naked full-length BPV-1 genome. BPV-1 virions reliably induced transient sarcoid-like skin tumours in all horses, whereas injection with DNA-based inocula failed to induce lesions. This result confirmed earlier findings supporting that intact virions are required to produce infection and associated disease in horses, and that intradermal inoculation of horses with virion constitutes a robust infection model. Based on these preliminary findings, we now propose to address the protective potential of BPV-1 L1 VLPs in horses, hypothesising that this vaccine candidate will prevent pseudo-tumour formation or significantly reduce the size and/or number of lesions. To this aim, 42 non-infected foals will be assigned to 2 equivalent groups. Fourteen randomly selected horses from each group will be immunised with BPV-1 L1 VLPs on days 0 and 28. The remaining 7 horses per group will receive adjuvant only and serve as controls. In addition, the study will include 4 naive horses subjected to passive serum protein transfer, and 8 horses immunised in 2007. Then, all horses will be challenged by intradermal inoculation with BPV-1 or BPV-2 virions. Horses will then be clinically monitored for a minimum of 6 month. Tumours expected in the control group and skin biopsies, as well as blood samples collected from all individuals will be subjected to down-stream analyses.Provided that a substantial protection from pseudo-tumour formation can be achieved, BPV-1 L1 VLPs are envisaged to be routinely employed for prevention of BPV-1/-2-associated disease in equids.