Chimeric virus-like particles replacing the loop on the surface of VP60 from rabbit hemorrhagic disease virus (RHDV) provide protection against two serotypes of RHDV.

In recent years, the rabbit hemorrhagic disease virus 2(RHDV GI.2) has rapidly spread worldwide due to its broad natural host range, strong pathogenicity, and significant antigenic differences from the traditional RHDV1 (GI.1). The widespread prevalence of both GI.1 and GI.2 RHDV poses a serious threat to the healthy development of the global rabbit industry. Despite this, there is still a notable absence of effective multivalent or broad-spectrum vaccines for controlling RHD(GI.1 and GI.2). In the present study, we developed a broad-spectrum chimeric antigen vaccine using a substitution strategy targeting the surface loop of the main antigen protein VP60 of RHDV. The chimeric VP60 antigen, expressed by a recombinant baculovirus expression system, was successfully assembled into virus-like particles (VLPs). The VLPs exhibited typical natural virus size and morphology under an electron microscope. Immunization with chimeric VLPs effectively protected rabbits from lethal challenged by both virulent strains of RHDV, GI.1 and GI.2, showing an effect comparable to that of a mixture vaccine containing two wild-type VLPs. These findings demonstrate a promising strategy for developing a cost-effective and straightforward preparation process for broad-spectrum vaccine against RHD.