Self-Adjuvanting Lipoprotein Conjugate αGalCer-RBD Induces Potent Immunity against SARS-CoV‑2 and its Variants of Concern

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.