Antibodies generatedin vitroandin vivoelucidate design of a thermostable ADDomer COVID-19 nasal nanoparticle vaccine
Author:
Buzas DoraORCID, Bunzel H AdrianORCID, Staufer OskarORCID, Milodowski Emily JORCID, Edmunds Grace LORCID, Bufton Joshua CORCID, Vidana Mateo Beatriz VORCID, Yadav Sathish K NORCID, Gupta KapilORCID, Fletcher CharlotteORCID, Kavanagh Williamson MaiaORCID, Harrison Alexandra, Borucu UfukORCID, Capin JulienORCID, Francis OreORCID, Balchin Georgia, Hall Sophie, Vivoli Vega MirellaORCID, Durbesson FabienORCID, Vincentelli RenaudORCID, Roe JoeORCID, Wooldridge LindaORCID, Burt RachelORCID, Anderson J L RossORCID, Mulholland Adrian JORCID, Hare Jonathan, Bailey Mick, Davidson Andrew DORCID, Finn AdamORCID, Morgan David, Mann JamieORCID, Spatz JoachimORCID, Garzoni FredericORCID, Schaffitzel ChristianeORCID, Berger ImreORCID,
Abstract
AbstractCOVID-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 vitrogenerated 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.
Publisher
Cold Spring Harbor Laboratory
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