An adjuvanted SARS-CoV-2 RBD nanoparticle elicits neutralizing antibodies and fully protective immunity in aged mice
Year: 2021
Type: preprint
Abstract: SUMMARY 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.
Authors: Francesco Borriello, Etsuro Nanishi, Hyuk-Soo Seo, Timothy R. O’Meara, Marisa E. McGrath, Yoshine Saito, Robert E. Haupt, Jing Chen, Joann Diray-Arce, Kijun Song, Andrew Z Xu, Timothy M. Caradonna, Jared Feldman, Blake M. Hauser, Aaron G. Schmidt, Lindsey R. Baden, Robert K. Ernst, Carly Dillen, Stuart M. Weston, Robert M. Johnson, Holly L. Hammond, Jingyou Yu, Aiquan Chang, Luuk Hilgers, Peter Paul Platenburg, Sirano Dhe-Paganon, Dan H. Barouch, Al Ozonoff, Ivan Zanoni, Matthew B. Frieman, David J. Dowling, Ofer Levy
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: Massachusetts Consortium on Pathogen Readiness, Daiichi Sankyo Foundation of Life Science, National Institutes of Health, Defense Advanced Research Projects Agency, Biomedical Advanced Research and Development Authority, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, Daiichi Sankyo Europe
Awards: G1337636553, G1616927606, G1636177350, G1813434710, G2660878362, G2661265154, G2874983153, G3168374244, G3178909089, G3353571719, G3636384462, Leveraging immunostimulatory pathways that enhance BCG vaccination for the rational design of synthetic neonatal vaccine formulations, G4204734726, G4974038237, G5025110712, G5494131953, G5514976981, G561983004, G5746588685, G6100960918, G6321917404, G6879041785, G7002079835, G707340384, G7295645321, G7702613265, G7976262187, G8275439092, G9000005946, G9000006793, G9000007979, G9000030784, G9000155537, G9000269537, G9000283030, G9000314418, Type III interferon Control of Mucosal Immunity, Innate control of the inflammatory process during fungal infections
OpenAlex ID: W3196585962