Potent Neutralizing Antibodies Elicited by RBD-Fc-Based COVID-19 Vaccine Candidate Adjuvanted by the Th2-Skewing iNKT Cell Agonist.
J Med Chem
; 64(15): 11554-11569, 2021 08 12.
Article
in English
| MEDLINE | ID: covidwho-1316696
ABSTRACT
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 C202) 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 C202 induced a significantly higher titer of the neutralizing antibody than that of Alum.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Adjuvants, Immunologic
/
Natural Killer T-Cells
/
Antibodies, Neutralizing
/
Galactosylceramides
/
COVID-19 Vaccines
Topics:
Vaccines
Limits:
Animals
/
Female
/
Humans
Language:
English
Journal:
J Med Chem
Journal subject:
Chemistry
Year:
2021
Document Type:
Article
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