Details

Autor(en) / Beteiligte

• 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.

Titel

Rational Design of an Epstein-Barr Virus Vaccine Targeting the Receptor-Binding Site

Ist Teil von

• Cell, 2015-08, Vol.162 (5), p.1090-1100

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2015

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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. [Display omitted] [Display omitted] •Self-assembling nanoparticles present the conserved gp350 receptor-binding domain•The nanoparticles elicit more potent neutralizing antibodies than soluble gp350•These neutralizing antibodies predominantly target the CR2-binding site on gp350•The nanoparticles elicit potent neutralizing antibodies in mice and non-human primates Structurally designed EBV vaccine candidates based on self-assembling nanoparticles elicit potent and durable virus-neutralizing antibodies that target the receptor-binding site on the viral envelope protein gp350, a site of vulnerability, serving as a template to develop an EBV vaccine and providing a basis for immunofocusing through rational vaccine design.