An adjuvanted SARS-CoV-2 RBD nanoparticle elicits neutralizing antibodies and fully protective immunity in aged mice
Borriello, F.; Nanishi, E.; Seo, H.-S.; OMeara, T. R.; McGrath, M. E.; Saito, Y.; Haupt, R. E.; Chen, J.; Diray-Arce, J.; Song, K.; Xu, A. Z.; Caradonna, T. M.; Feldman, J.; Hauser, B. M.; Schmidt, A. G.; Baden, L. R.; Ernst, R. K.; Dillen, C.; Weston, S. M.; Johnson, R. M.; Hammond, H. L.; Yu, J.; Chang, A.; Hilgers, L.; Platenburg, P. P.; Dhe-Paganon, S.; Barouch, D. H.; Ozonoff, A.; Zanoni, I.; Frieman, M. B.; Dowling, D. J.; Levy, O.
Show abstract
Development of affordable and effective vaccines that can also protect vulnerable populations such as the elderly from COVID-19-related morbidity and mortality is a public health priority. Here we took a systematic and iterative approach by testing several SARS-CoV-2 protein antigens and adjuvants to identify a combination that elicits neutralizing antibodies and protection in young and aged mice. In particular, SARS-CoV-2 receptorbinding domain (RBD) displayed as a protein nanoparticle (RBD-NP) was a highly effective antigen, and when formulated with an oil-in-water emulsion containing Carbohydrate fatty acid MonoSulphate derivative (CMS) induced the highest levels of cross-neutralizing antibodies compared to other oil-in-water emulsions or AS01B. Mechanistically, CMS induced antigen retention in the draining lymph node (dLN) and expression of cytokines, chemokines and type I interferon-stimulated genes at both injection site and dLN. Overall, CMS:RBD-NP is effective across multiple age groups and is an exemplar of a SARS-CoV-2 subunit vaccine tailored to the elderly.
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