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ABSTRACT
COVID-19 continues to damage populations, communities and economies worldwide. Vaccines have reduced COVID-19-related hospitalisations and deaths, primarily in developed countries. Persisting infection rates, and highly transmissible SARS-CoV-2 Variants of Concern (VOCs) causing repeat and breakthrough infections, underscore the ongoing need for new treatments to achieve a global solution. Based on ADDomer, a self-assembling protein nanoparticle scaffold, we created ADDoCoV, a thermostable COVID-19 candidate vaccine displaying multiple copies of a SARS-CoV-2 receptor binding motif (RBM)-derived epitope. In vitro generated neutralising nanobodies combined with molecular dynamics (MD) simulations and electron cryo-microscopy (cryo-EM) established authenticity and accessibility of the epitopes displayed. A Gigabody comprising multimerized nanobodies prevented SARS-CoV-2 virion attachment with picomolar EC50. Antibodies generated by immunising mice cross-reacted with VOCs including Delta and Omicron. Our study elucidates nasal administration of ADDomer-based nanoparticles for active and passive immunisation against SARS-CoV-2 and provides a blueprint for designing nanoparticle reagents to combat respiratory viral infections.
Sujets)

Texte intégral: Disponible Collection: Preprints Base de données: bioRxiv Sujet Principal: Infections de l'appareil respiratoire / Syndrome respiratoire aigu sévère / Douleur paroxystique / COVID-19 langue: Anglais Année: 2023 Type de document: Preprint

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Texte intégral: Disponible Collection: Preprints Base de données: bioRxiv Sujet Principal: Infections de l'appareil respiratoire / Syndrome respiratoire aigu sévère / Douleur paroxystique / COVID-19 langue: Anglais Année: 2023 Type de document: Preprint