Potent Neutralizing Antibodies Elicited by RBD-Fc-Based COVID-19 Vaccine Candidate Adjuvanted by the Th2-Skewing iNKT Cell Agonist

The
development of a safe and effective COVID-19 vaccine is of
paramount importance to terminate the current pandemic. An adjuvant
is crucial for improving the efficacy of the subunit COVID19 vaccine.
α-Galactosylceramide (αGC) is a classical iNKT cell agonist
which causes the rapid production of Th1- and Th2-associated cytokines;
we, therefore, expect that the Th1- or Th2-skewing analogues of αGC
can better enhance the immunogenicity of the receptor-binding domain
in the spike protein of SARS-CoV-2 fused with the Fc region of human
IgG (RBD-Fc). Herein, we developed a universal synthetic route to
the Th1-biasing (α-C-GC) and Th2-biasing (OCH and C20:2) analogues.
Immunization of mice demonstrated that αGC-adjuvanted RBD-Fc
elicited a more potent humoral response than that observed with Alum
and enabled the sparing of antigens. Remarkably, at a low dose of
the RBD-Fc protein (2 μg), the Th2-biasing agonist C20:2 induced
a significantly higher titer of the neutralizing antibody than that
of Alum.