Protection Against Rabbit Hemorrhagic Disease Virus Strains: Efficacy of a New Commercial Recombinant RHDV2 Capsid Protein VP60 Vaccine

Background/Objectives: Rabbit hemorrhagic disease (RHD) is an incurable, highly contagious disease caused by different RHD virus (RHDV) strains, such as the coexisting RHDV2 and classical RHDV. Disease control is based on vaccination using different or polyvalent vaccines. This study assessed the protective efficacy, onset of immunity (OOI), and duration of immunity (DOI) of a new recombinant vaccine containing a single active substance developed to target both strains: against RDHV2, highly virulent RDHV2 (hvRHDV2), and classical RDHV strains. Methods: This study included six randomized, controlled, blinded trials in clinically healthy New Zealand White rabbits. Rabbits were grouped to receive the recombinant vaccine or placebo (1:1 ratio) and challenged with RHDV2 (2¹⁵ hemagglutination [HA], infective dose; n = 39 for duration and n = 43 for onset), hvRHDV2 (2¹⁵ HA; n = 48 and n = 40), or classical RHDV (2¹² hemagglutination [HA], infective dose; n = 20 and n = 22) strains to evaluate OOI and DOI. Results: Rabbits receiving the vaccine showed a lower mortality than those receiving placebo upon challenge with any of the three strains. OOI trials showed that vaccinated rabbits exhibited higher levels of antibodies against RHDV2 than controls seven days post-vaccination. DOI trials revealed that, compared with controls, vaccinated rabbits had increased levels of antibodies against RHDV2 across all time points assessed, at least until the day of the viral challenge with any of the RHDV strains (approximately 12 months post-vaccination). Conclusions: This recombinant vaccine is the first to show a durable and robust protection against all tested strains, including the RHDV2, hvRHDV2, and classical RHDV strains, underscoring its potential as a comprehensive tool for RHD prevention.