Synthetic self-assembling ADDomer platform for highly efficient vaccination by genetically encoded multiepitope display

通过基因编码的多表位展示实现高效疫苗接种的合成自组装 ADDomer 平台

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作者:Charles Vragniau, Joshua C Bufton, Frédéric Garzoni, Emilie Stermann, Fruzsina Rabi, Céline Terrat, Mélanie Guidetti, Véronique Josserand, Matt Williams, Christopher J Woods, Gerardo Viedma, Phil Bates, Bernard Verrier, Laurence Chaperot, Christiane Schaffitzel, Imre Berger, Pascal Fender

Abstract

Self-assembling virus-like particles represent highly attractive tools for developing next-generation vaccines and protein therapeutics. We created ADDomer, an adenovirus-derived multimeric protein-based self-assembling nanoparticle scaffold engineered to facilitate plug-and-play display of multiple immunogenic epitopes from pathogens. We used cryo-electron microscopy at near-atomic resolution and implemented novel, cost-effective, high-performance cloud computing to reveal architectural features in unprecedented detail. We analyzed ADDomer interaction with components of the immune system and developed a promising first-in-kind ADDomer-based vaccine candidate to combat emerging Chikungunya infectious disease, exemplifying the potential of our approach.

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