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J Med Chem
. 2022 Jan 24.
doi: 10.1021/acs.jmedchem.1c02000. Online ahead of print.
Self-Adjuvanting Lipoprotein Conjugate αGalCer-RBD Induces Potent Immunity against SARS-CoV-2 and its Variants of Concern
Jian Wang 1 , Yu Wen 1 , Shi-Hao Zhou 1 , Hai-Wei Zhang 2 , Xiao-Qian Peng 1 , Ru-Yan Zhang 1 , Xu-Guang Yin 1 , Hong Qiu 3 , Rui Gong 2 , Guang-Fu Yang 1 , Jun Guo 1
Affiliations
- PMID: 35073081
- DOI: 10.1021/acs.jmedchem.1c02000
Abstract
Safe and effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants are the best approach to successfully combat the COVID-19 pandemic. The receptor-binding domain (RBD) of the viral spike protein is a major target to develop candidate vaccines. α-Galactosylceramide (αGalCer), a potent invariant natural killer T cell (iNKT) agonist, was site-specifically conjugated to the N-terminus of the RBD to form an adjuvant-protein conjugate, which was anchored on the liposome surface. This is the first time that an iNKT cell agonist was conjugated to the protein antigen. Compared to the unconjugated RBD/αGalCer mixture, the αGalCer-RBD conjugate induced significantly stronger humoral and cellular responses. The conjugate vaccine also showed effective cross-neutralization to all variants of concern (B.1.1.7/alpha, B.1.351/beta, P.1/gamma, B.1.617.2/delta, and B.1.1.529/omicron). These results suggest that the self-adjuvanting αGalCer-RBD has great potential to be an effective COVID-19 vaccine candidate, and this strategy might be useful for designing various subunit vaccines.