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

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.