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J Med Chem . Self-Adjuvanting Lipoprotein Conjugate αGalCer-RBD Induces Potent Immunity against SARS-CoV-2 and its Variants of Concern

tetano

Editor, Senior Moderator
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[SUP] 1 [/SUP], Yu Wen[SUP] 1 [/SUP], Shi-Hao Zhou[SUP] 1 [/SUP], Hai-Wei Zhang[SUP] 2 [/SUP], Xiao-Qian Peng[SUP] 1 [/SUP], Ru-Yan Zhang[SUP] 1 [/SUP], Xu-Guang Yin[SUP] 1 [/SUP], Hong Qiu[SUP] 3 [/SUP], Rui Gong[SUP] 2 [/SUP], Guang-Fu Yang[SUP] 1 [/SUP], Jun Guo[SUP] 1 [/SUP]



Affiliations

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.
 
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