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

By M. Kanekiyo, Wei Bu, M. Joyce, G. Meng, J. Whittle, U. Baxa, Takuya Yamamoto, Sandeep N. Narpala, J. Todd, S. Rao and 7 more. 2015

346 citations recorded by the source corpus.

SUMMARY 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.

Subfields: Epidemiology, Oncology, Virology

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Epidemiology

1. F. Sallusto
2. Ralph S. Baric
3. A. Lanzavecchia
4. A. Walls
5. D. Veesler
6. M. Kanekiyo

In Oncology

1. F. Sallusto
2. A. Lanzavecchia

In Virology

1. Neil P. King
2. F. Sallusto
3. A. Lanzavecchia

Citations in the corpus

• Elicitation of Potent Neutralizing Antibody Responses by Designed Protein Nanoparticle Vaccines for SARS-CoV-2 (2020, positive): “, 2020), as well as a nanoparticle vaccine candidate for Epstein-Barr virus conceptually similar to our RBD nanoparticle immunogens that displayed the CR2-binding domain of gp350 (Kanekiyo et al., 2015).”
• Induction of Potent Neutralizing Antibody Responses by a Designed Protein Nanoparticle Vaccine for Respiratory Syncytial Virus (2019, background): “In all cases, immunogenicity of the antigen was increasedbymultivalent presentation, and in somecases, an epitope-focusingeffectwasobserved inwhichpotent neutralizing epitopeswere preferentially targeted (Duan et al., 2018; Kanekiyo et al., 2015; Yassine et al., 2015).”
• New Vaccine Design and Delivery Technologies (2019, background): “In some cases, simple elimination of undesired portions of the antigen, usually along domain boundaries, can be used to produce minimal antigens that are both structurally and antigenically intact [46] [47] [48] [49] .”
• Development of a Pan-H1 Influenza Vaccine (2018, neutral): “HA (11), EBV gp220 (25), and HIV envelope (26).”
• Self-assembling protein nanoparticles in the design of vaccines (2015, positive): “In preclinical studies, the chimeric nanoparticle-gp350 antigens elicited 10- to 100-fold more potent virus-neutralizing antibody titers than the soluble gp350 antigens alone [95].”