Immunization with a Self-Assembled Nanoparticle Vaccine Elicits Potent Neutralizing Antibody Responses against EBV...

Epstein-Barr virus (EBV) infection is a global health concern infecting over 90% of the population. However, there is no currently available vaccine. EBV primarily infects B cells, where the major glycoprotein 350 (gp350) is the main target of neutralizing antibodies. Given the advancement of nanoparticle vaccines, we describe rationally designed vaccine modalities presenting 60 copies of gp350 on self-assembled nanoparticles in a repetitive array. In a mouse model, gp350s on lumazine synthase (LS) and I3-01 adjuvanted with MF59 or aluminum hydroxide (Alhydrogel) elicited over 65- to 133-fold higher neutralizing antibody titers than the corresponding gp350 monomer to EBV. Furthermore, immunization with gp350D₁₂₃-LS and gp350D₁₂₃-I3-01 vaccine induced a Th2-biased response. For the nonhuman primate model, gp350D₁₂₃-LS in MF59 elicited higher titers of total IgG and neutralizing antibodies than the monomeric gp350D₁₂₃. Overall, these results support gp350D₁₂₃-based nanoparticle vaccine design as a promising vaccine candidate for potent protection against EBV infection.