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

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...

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Detalles Bibliográficos
Autores principales: Vragniau, Charles, Bufton, Joshua C., Garzoni, Frédéric, Stermann, Emilie, Rabi, Fruzsina, Terrat, Céline, Guidetti, Mélanie, Josserand, Véronique, Williams, Matt, Woods, Christopher J., Viedma, Gerardo, Bates, Phil, Verrier, Bernard, Chaperot, Laurence, Schaffitzel, Christiane, Berger, Imre, Fender, Pascal
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6763337/
https://www.ncbi.nlm.nih.gov/pubmed/31620562
http://dx.doi.org/10.1126/sciadv.aaw2853
Descripción
Sumario: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.