ジャーナル: Cell / 年: 2015 タイトル: Rational Design of an Epstein-Barr Virus Vaccine Targeting the Receptor-Binding Site. 著者: 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 ...著者: 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 / 要旨: 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 ...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.