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

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 gp350D(123 )LS and gp350D(123)-I3-01 vaccine induced a Th2-biased response. For the nonhuman primate model, 350D(123)-LS in MF59 elicited higher titers of total IgG and neutralizing antibodies than the monomeric gp350D(123). Overall, these results support gp350D(123)-based nanoparticle vaccine design as a promising vaccine candidate for potent protection against EBV infection.

Automated summary

This study utilized self-assembled nanoparticles presenting copies of gp350 to design a promising EBV vaccine candidate that could induce higher neutralizing antibody titers compared to monomeric gp350 vaccines. Results from animal experiments showed that this vaccine design could effectively trigger neutralizing antibody production, and in nonhuman primate models, it demonstrated potential protection against EBV infection.