Potential of a BPV1 L1 VLP vaccine to prevent BPV1- or BPV2-induced pseudo-sarcoid formation and safety and immunogenicity of EcPV2 L1 VLPs in the horse

We have previously shown that immunization of horses with BPV1 L1 virus-like particles (VLP) is safe and highly immunogenic, and that bovine papillomavirus types 1 and 2 (BPV1, BPV2) are closely related serotypes. Here we evaluated the protective potential of a BPV1 L1 VLP vaccine against experimental BPV1 and BPV2 challenge, and studied the safety and immunogenicity of a bivalent EcPV2/BPV1 L1 VLP vaccine. Fourteen healthy horses were immunized with BPV1 L1 VLPs (100 µg/injection) plus adjuvant on days 0 and 28, whilst seven remained unvaccinated. On day 42, all 21 horses were challenged intradermally at ten sites of the neck with 107 BPV1 virions per injection. In analogy, 14 horses immunized twice with EcPV2 plus BPV1 L1 VLPs (50 µg each) and seven control animals were challenged with 107 BPV2 virions/injection. Immunization with BPV1 L1 VLPs alone induced a robust antibody response (day-42 median titre: 12,800) and BPV1-inoculated skin remained unchanged in 13/14 vaccinated horses. Immunization with the bivalent vaccine was safe, resulted in lower median day-42 antibody titres of 400 for BPV1, and 1600 for EcPV2, and conferred significant yet incomplete cross-protection from BPV2-induced tumour formation, with 11/14 horses developing small, short-lived papules. Control horses developed pseudo-sarcoids at all inoculation sites. The monovalent BPV1 L1 VLP vaccine proved highly effective in protecting horses from BPV1-induced pseudo-sarcoid formation. Incomplete protection from BPV2-induced tumour development conferred by the bivalent vaccine is due to the poorer immune response by immune interference or lower cross-neutralization titres to heterologous BPV2 virions.