Author:
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
Abstract
SUMMARYDevelopment 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.
Publisher
Cold Spring Harbor Laboratory