An adjuvanted SARS-CoV-2 RBD nanoparticle elicits neutralizing antibodies and fully protective immunity in aged mice
F. Borriello, E. Nanishi, H.-S. Seo, T. R. OMeara, M. E. McGrath, Y. Saito, R. E. Haupt, J. Chen, J. Diray-Arce, K. Song, A. Z. Xu, T. M. Caradonna, J. Feldman, B. M. Hauser, A. G. Schmidt, L. R. Baden, R. K. Ernst, C. Dillen, S. M. Weston, R. M. Johnson, H. L. Hammond, J. Yu, A. Chang, L. Hilgers, P. P. Platenburg, , O. Levy
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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