Self-assembling Epstein-Barr virus glycoprotein nanoparticle vaccines elicit antibodies that potently neutralize virus infection of B cells and epithelial cells

Authors

• W Bu
• M Kanekiyo
• BS Graham
• GJ Nabel
• JI Cohen

Abstract

Antibodies to EBV glycoprotein gp350, gH/gL and gp42 are present in sera of EBV seropositive persons and neutralize virus infection of B cells and epithelial cells. gp350 antibodies are the predominant antibodies in human plasma that neutralize B cell infection, followed by gH/gL and gp42 antibodies. In contrast, gH/gL antibodies are the predominant antibodies that neutralize epithelial cell infection. Since B cell and epithelial cell infection are important for the normal EBV life cycle, effective EBV vaccines should elicit antibodies that neutralize infection of both of these cell types. Here we report self-assembling nanoparticle-based EBV vaccine candidates to present gp350, gH/gL, or gH/gL/gp42 in a symmetrically ordered repetitive manner to improve immunogenicity. The immunogenicity of EBV glycoprotein nanoparticles and soluble glycoproteins was compared in mice. We found that neutralizing antibody titers elicited by immunizing mice with gp350-nanoparticles were >100-fold higher than soluble gp350. About 50% of the antibodies elicited by gp350-nanoparticles targeted the EBV receptor binding site, compared with ~5% of the antibodies induced by soluble gp350. Mice immunized with gH/gL-nanoparticles had neutralizing antibody titers that were >500-fold higher than mice immunized with soluble gH/gL for B cell and epithelial cell infection. Neutralizing antibody titers elicited by gH/gL/gp42-nanoparticles were ~100-fold higher and >500-fold higher than the titer induced by soluble gH/gL/gp42 for B cell and epithelial cell infection, respectively. In conclusion, we demonstrate that EBV glycoprotein nanoparticles are highly immunogenic, elicit higher neutralizing antibody titers than their soluble counterparts, and are promising vaccine candidates to prevent EBV infection and/or disease.

Scientific Focus Area: Virology

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