A novel replication-deficient FCV vaccine provides strong immune protection in cats

ABSTRACT Feline calicivirus (FCV) belongs to the family Caliciviridae, which includes important animal and human pathogens such as human norovirus and rabbit hemorrhagic disease virus. The fast evolution and great diversity of FCV make it highly difficult to develop vaccines that can induce sterilizing immunity. In this study, we evaluated the efficacy of a vaccine candidate generated via a replication-deficient vaccine strategy. Immunization with the vaccine generated a high level of neutralizing antibodies and highly reduced clinical outcomes against the challenge with a homologous virulent systemic feline calicivirus (VS-FCV) strain. Moreover, the VP1 gene of the vaccine was replaced with that derived from a heterologous virus strain. Vaccination with two combined virus constructs containing genetically distant VP1 genes led to the generation of broad neutralizing antibodies against FCV strains in cats. Notably, this replication-deficient FCV has the potential to serve as a viral vector vaccine, enabling the delivery of a foreign gene with stable genetics. In summary, this vaccine strategy holds great promise for developing safe, effective, and multivalent vaccines to prevent and control calicivirus infection. IMPORTANCE FCV is one of the leading causes of respiratory diseases in cats. Over the last 20 years, certain strains evolved into VS-FCV, with severe symptoms and increased fatality. Updating and developing vaccines promptly are essential. Here, we employed reverse genetics to partially delete the VP2 gene of FCV, rescuing the replication-deficient vaccine candidate rHBDL2 FCV-△VP2. Immunization with this candidate generated high levels of neutralizing antibodies against FCV strains and significantly reduced clinical symptoms. Furthermore, the adaptability of this replication-defective FCV platform holds potential for the development of viral vector vaccines as well as multivalent vaccines, which are also crucial for the prevention and control of other calicivirus infections.