Preclinical study of formulated recombinant nucleocapsid protein, the receptor binding domain of the spike protein, and truncated spike (S1) protein as vaccine candidates against COVID-19 in animal models.
Mol Immunol
; 149: 107-118, 2022 09.
Article
in English
| MEDLINE | ID: covidwho-1907590
ABSTRACT
BACKGROUND:
In this pre-clinical study, we designed a candidate vaccine based on severe acute respiratory syndrome-related -coronavirus 2 (SARS-CoV-2) antigens and evaluated its safety and immunogenicity.METHODS:
SARS-CoV-2 recombinant protein antigens, including truncated spike protein (SS1, lacking the N-terminal domain of S1), receptor-binding domain (RBD), and nucleoprotein (N) were used. Immunization program was performed via injection of RBD, SS1 +RBD, and SS1 +N along with different adjuvants, Alum, AS03, and Montanide at doses of 0, 40, 80, and 120 µg at three-time points in mice, rabbits, and primates. The humoral and cellular immunity were analyzed by ELISA, VNT, splenocyte cytokine assay, and flow cytometry.RESULTS:
The candidate vaccine produced strong IgG antibody titers at doses of 80 and 120 µg on days 35 and 42. Even though AS03 and Montanide produced high-titer antibodies compared to Alum adjuvant, these sera did not neutralize the virus. Strong virus neutralization was recorded during immunization with SS1 +RBD and RBD with Alum. AS03 and Montanide showed a strong humoral and cellular immunity; however, Alum showed mild to moderate cellular responses. Ultimately, no cytotoxicity and pathologic change were observed.CONCLUSION:
These findings strongly suggest that RBD with Alum adjuvant is highly immunogenic as a potential vaccine.Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Viral Vaccines
/
COVID-19
Type of study:
Experimental Studies
/
Prognostic study
Topics:
Vaccines
Limits:
Animals
Language:
English
Journal:
Mol Immunol
Year:
2022
Document Type:
Article
Affiliation country:
J.molimm.2022.06.007
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