Editors' ChoiceVaccines

A vaccine to kiss EBV goodbye

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Science Translational Medicine  24 Apr 2019:
Vol. 11, Issue 489, eaax1729
DOI: 10.1126/scitranslmed.aax1729

Abstract

A nanoparticle Epstein-Barr virus glycoprotein gH/gL vaccine elicits antibodies that mediate cell type–independent protection from infection.

The ubiquitous herpesvirus oncogenic Epstein-Barr virus (EBV) not only causes mononucleosis but is also associated with approximately 200,000 cases of cancer each year. EBV infection occurs within both epithelial and B cells. gH, gL, and gp42 compose the viral fusion complex. Epithelial cells are infected following interactions with gH/gL. gp42 is also involved in EBV entry of B cells which is initiated by glycoprotein gp350. The majority of identified serum-neutralizing antibodies that block B cell infection target the gp350 antigen. As such, the majority of EBV vaccine trials have used gp350 as the sole immunizing antigen. However, to date, no effective vaccine against EBV has been developed.

To reimagine EBV vaccines, Bu and colleagues assessed the contribution of gp350, gH/gL, and gp42- targeting antibodies for neutralization of both epithelial and B cell infection. They discovered that the overwhelming majority of neutralizing antibodies preventing epithelial cell infection targeted gH/gL. Anti-gH/gL antibodies also contributed to neutralization of B cell infection, thus identifying antigen targets that may mediate cell type–independent protection from infection. To formally assess the potential of gH/gL as a vaccine candidate, authors generated both gH/gL and gH/gL/gp42 self-assembling ferritin nanoparticle vaccines. In mice and nonhuman primates, these nanoparticle vaccines induced high titers of both epithelial and B cell–protective antibodies. Validating these findings, induced antibodies appeared to target a site on gH/gL critical for virus fusion.

Because EBV is restricted to humans, a viral challenge cannot be performed in animal models; protection from infection will only be shown with clinical trials. With a central importance of both epithelial and B cells in EBV replication, these findings open exciting new avenues for the development of effective EBV vaccines. With most EBV-associated cancers occurring within epithelial malignancies, these reimagined vaccine approaches may prevent not only infection but also EBV-associated cancer disease burdens.

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