Rational Design of an Epstein-Barr Virus Vaccine Targeting the Receptor-Binding Site
Masaru Kanekiyo, Wei Bu, M Gordon Joyce, Geng Meng, James R R Whittle, Ulrich Baxa, Takuya Yamamoto, Sandeep Narpala, John-Paul Todd, Srinivas S Rao, Adrian B McDermott, Richard A Koup, Michael G Rossmann, John R Mascola, Barney S Graham, Jeffrey I Cohen, Gary J Nabel, Masaru Kanekiyo, Wei Bu, M Gordon Joyce, Geng Meng, James R R Whittle, Ulrich Baxa, Takuya Yamamoto, Sandeep Narpala, John-Paul Todd, Srinivas S Rao, Adrian B McDermott, Richard A Koup, Michael G Rossmann, John R Mascola, Barney S Graham, Jeffrey I Cohen, Gary J Nabel
Abstract
Epstein-Barr virus (EBV) represents a major global health problem. Though it is associated with infectious mononucleosis and ∼200,000 cancers annually worldwide, a vaccine is not available. The major target of immunity is EBV glycoprotein 350/220 (gp350) that mediates attachment to B cells through complement receptor 2 (CR2/CD21). Here, we created self-assembling nanoparticles that displayed different domains of gp350 in a symmetric array. By focusing presentation of the CR2-binding domain on nanoparticles, potent neutralizing antibodies were elicited in mice and non-human primates. The structurally designed nanoparticle vaccine increased neutralization 10- to 100-fold compared to soluble gp350 by targeting a functionally conserved site of vulnerability, improving vaccine-induced protection in a mouse model. This rational approach to EBV vaccine design elicited potent neutralizing antibody responses by arrayed presentation of a conserved viral entry domain, a strategy that can be applied to other viruses.
Copyright © 2015 Elsevier Inc. All rights reserved.
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References
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