A Chimeric Virus-Like Particle Vaccine Presenting an Immunodominant Epitope of gB Elicited Potent Neutralizing Antibodies against EBV Infection In Vitro and In Vivo

Epstein–Barr Virus (EBV) as the first characterized tumorigenic virus in humans causes heavy disease burdens. An effective vaccine is urgently needed to block EBV infection. Glycoprotein B (gB) is the essential fusogen for EBV infection of all susceptible cell types. We previously demonstrated that neutralizing antibody 3A3 targeting gB effectively blocked EBV infection in a humanized mouse model, indicating that the epitope recognized by 3A3 is the potential immunogen candidate. Hence, we rationally designed a chimeric virus-like particle (cVLP) vaccine based on the hepatitis B core antigen (HBc149) to display gB peptide, αB, recognized by 3A3 (149-αB cVLP). The engineered 149-αB cVLP vaccine self-assembled into spherical particles presenting multiple copies of αB peptide. The 149-αB cVLP vaccine induced much higher antibody titers against αB peptides than gB protein immunization. Importantly, sera antibodies elicited by the 149-αB cVLP vaccine more efficiently blocked EBV infection and membrane fusion of epithelial cells and B cells. Sera from 149-αB cVLP vaccine-immunized rabbits conferred 100% protection against EBV infection in a humanized mouse model. We demonstrated that the 149-αB cVLP vaccine induced potent antigen-specific protective immune responses and shed light on the research of peptide-based vaccines against EBV infection.