Antibodies generated in vitro and in vivo elucidate design of a thermostable ADDomer COVID-19 nasal nanoparticle vaccine

Buzas, D.; Bunzel, H. A.; Staufer, O.; Milodowski, E.; Edmonds, G.; Vidana Matteo, b.; Berger Schaffitzel, C.; Yadav, S.; Gupta, K.; Fletcher, C.; Kavanagh Williamson, M.; Harrison, A.; Borucu, U.; Capin, J.; Francis, O.; Balchin, G.; Hall, S.; Vivoli Vega, M.; Durbesson, F.; Vincentelli, R.; Roe, J.; Wooldridge, L.; Burt, R.; Anderson, R.; Mulholland, A. J.; Hare, J.; Bailey, M.; Davidson, A.; Finn, A.; Morgan, D.; Mann, J.; SPatz, J.; Garzoni, F.; Bufton, J.; Berger, I.

doi:10.1101/2023.03.17.533092

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bioRxiv · 10.1101/2023.03.17.533092

Antibodies generated in vitro and in vivo elucidate design of a thermostable ADDomer COVID-19 nasal nanoparticle vaccine

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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.

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Buzas, D., Bunzel, H. A., Staufer, O., Milodowski, E., Edmonds, G., Vidana Matteo, b., Berger Schaffitzel, C., Yadav, S., Gupta, K., Fletcher, C., Kavanagh Williamson, M., Harrison, A., Borucu, U., Capin, J., Francis, O., Balchin, G., Hall, S., Vivoli Vega, M., Durbesson, F., Vincentelli, R., Roe, J., Wooldridge, L., Burt, R., Anderson, R., Mulholland, A. J., Hare, J., Bailey, M., Davidson, A., Finn, A., Morgan, D., Mann, J., SPatz, J., Garzoni, F., Bufton, J., Berger, I.. 2023-03-17. Antibodies generated in vitro and in vivo elucidate design of a thermostable ADDomer COVID-19 nasal nanoparticle vaccine. https://doi.org/10.1101/2023.03.17.533092

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