An adjuvanted SARS-CoV-2 RBD nanoparticle elicits neutralizing antibodies and fully protective immunity in aged mice

Borriello, Francesco; Nanishi, Etsuro; Seo, Hyuk-Soo; O’Meara, Timothy R.; McGrath, Marisa E.; Saito, Yoshine; Haupt, Robert E.; Chen, Jing; Diray-Arce, Joann; Song, Kijun; Xu, Andrew Z; Caradonna, Timothy M.; Feldman, Jared; Hauser, Blake M.; Schmidt, Aaron G.; Baden, Lindsey R.; Ernst, Robert K.; Dillen, Carly; Weston, Stuart M.; Johnson, Robert M.; Hammond, Holly L.; Yu, Jingyou; Chang, Aiquan; Hilgers, Luuk; Platenburg, Peter Paul; Dhe-Paganon, Sirano; Barouch, Dan H.; Ozonoff, Al; Zanoni, Ivan; Frieman, Matthew B.; Dowling, David J.; Levy, Ofer

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.