Adjuvant properties of baculovirus enhance the immunogenicity and protective efficacy of foot-and-mouth disease virus-like particles vaccines in mice.

Foot-and-mouth disease (FMD) is one of the most economically relevant livestock diseases worldwide due to the rapid spread of its etiological agent, Foot-and-mouth Disease Virus (FMDV), and the severe economic losses associated with outbreaks. Virus-like particle (VLP)-based vaccines represent a safe alternative to conventional inactivated vaccines; however, their limited immunogenicity remains a drawback. Baculoviruses naturally infect insects and are non-replicative in vertebrates, possess strong intrinsic immunostimulatory properties and can function as vaccine adjuvants. In this study, we designed a rational vaccine strategy based on FMDV VLPs combined with baculovirus as an adjuvant and evaluated the immune response in a murine challenge model. FMDV VLPs were successfully produced in insect pupae and characterized by Western blot, transmission electron microscopy, and ELISA. Co-administration of baculovirus and FMDV VLPs significantly enhanced the humoral immune response, leading to higher antibody levels compared to VLPs alone. Moreover, vaccinated animals exhibited partial protection characterized by reduced clinical signs, improved body weight maintenance, and increased survival compared to control groups following viral challenge. Additional in vitro studies in dendritic cells (DC) identified baculovirus as the main immunostimulatory component of the formulation, promoting cellular activation. Overall, these findings support the use of baculovirus as an adjuvant for FMDV VLP-based vaccines, improving immunogenicity and promoting partial protection in this murine proof-of-concept model. These findings support the potential of this platform as a promising and versatile strategy for the development of safer and more cost-effective veterinary vaccines.