Selected article for: "major problem and mouse model"
Author: 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.; Nabel, Gary J.
Title: Rational Design of an Epstein-Barr Virus Vaccine Targeting the Receptor-Binding Site
  • Cord-id: 43jz55qs
  • Document date: 2015_8_1
    • ID: 43jz55qs
    Snippet: Epstein-Barr virus (EBV) represents a major global health problem. Though it is associated with infectious mononucleosis and over 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 o
    Document: Epstein-Barr virus (EBV) represents a major global health problem. Though it is associated with infectious mononucleosis and over 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 improved vaccine-induced protection in a mouse model by targeting a functionally conserved site of vulnerability with 10- to 100-fold increased neutralization compared to soluble gp350. This rational approach to EBV vaccine design elicited potent neutralizing antibody responses by focusing on a conserved viral entry domain, a strategy that can be applied to other viruses.

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