Editors' ChoiceNanotechnology

Nanoparticles, macroplanning

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Science Translational Medicine  16 Sep 2015:
Vol. 7, Issue 305, pp. 305ec157
DOI: 10.1126/scitranslmed.aad3614

Epstein-Barr virus (EBV) infection causes infectious mononucleosis and over 200,000 incidents of cancer annually; however, there is currently no vaccine available. Now, researchers are thinking small to address this big problem. Kanekiyo et al. used nanotechnology combined with a deep knowledge of structural biology to present an EBV antigen, gp350, with high immunogenicity. The result was not only a potential vaccine that optimally presents potent neutralizing antibodies, but also a model for future research.

Kanekiyo et al. realized that a more effective EBV vaccine demanded a rational, synthetic approach. Therefore, they presented monomeric antigens on the surface of self-assembling nanoparticles with either ferritin on encapsulin as the platform, resulting in evenly distributed antigen-attachment sites across the nanoparticle surface. Their rational approach displayed different domains of gp350 in a symmetric array, resulting in potent neutralizing antibodies. The nanoparticle truncation variant D123-ferritin was stably expressed and formed effective T cell–mediated bonds with B cells that express the high amounts of gp350 receptor CR2, effectively presenting as the viral pathogen. When injected into mice along with soluble gp350 derivatives, the nanoparticle vaccine elicited immune responses that dwarfed previous methods, and antibody titers only increased following a second dose. Further testing in rhesus macaques also showed improved immune response, even though the primates already held cross-neutralizing EBV antibodies.

These studies demonstrate the promise of this rationally designed vaccine in mice, although future studies with larger sample sizes will be needed to fuel translational studies. Moreover, although the impact on macaques was less dramatic compared with soluble gp350, this model provides a great starting point for optimization of a human dosing regimen. Still, Kanekiyo et al. have shown the power of using structural biology, typically seen in small molecule design, to rationally design a nanotechnology vaccine. Generally, this rational approach could allow synthetically (re)designed vaccines for the most stubborn viruses, perhaps with the promising use of ferritin-based scaffolding. For nanotechnology and vaccines, planning the tiniest parts of the tiniest particles can have the largest of impacts.

M. Kanekiyo et al., Rational design of an Epstein-Barr virus vaccine targeting the receptor-binding site. Cell 162, 1090–1100 (2015). [Abstract]

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