1. Rational Design of an Epstein-Barr Virus Vaccine Targeting the Receptor-Binding Site.
- Author
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Kanekiyo, Masaru, Bu, Wei, Joyce, M. Gordon, Meng, Geng, Whittle, James R.R., Baxa, Ulrich, Yamamoto, Takuya, Narpala, Sandeep, Todd, John-Paul, Rao, Srinivas S., McDermott, Adrian B., Koup, Richard A., Rossmann, Michael G., Mascola, John R., Graham, Barney S., Cohen, Jeffrey I., and Nabel, Gary J.
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EPSTEIN-Barr virus , *VIRAL vaccines , *TARGETED drug delivery , *BINDING sites , *CELL receptors - Abstract
Summary 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. PaperClip [ABSTRACT FROM AUTHOR]
- Published
- 2015
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