A triple-RBD-based mucosal vaccine provides broad protection against SARS-CoV-2 variants of concern.
Cell Mol Immunol
; 19(11): 1279-1289, 2022 Nov.
Article
in English
| MEDLINE | ID: covidwho-2062197
ABSTRACT
The rapid mutation and spread of SARS-CoV-2 variants urge the development of effective mucosal vaccines to provide broad-spectrum protection against the initial infection and thereby curb the transmission potential. Here, we designed a chimeric triple-RBD immunogen, 3Ro-NC, harboring one Delta RBD and two Omicron RBDs within a novel protein scaffold. 3Ro-NC elicits potent and broad RBD-specific neutralizing immunity against SARS-CoV-2 variants of concern. Notably, intranasal immunization with 3Ro-NC plus the mucosal adjuvant KFD (3Ro-NC + KFDi.n) elicits coordinated mucosal IgA and higher neutralizing antibody specificity (closer antigenic distance) against the Omicron variant. In Omicron-challenged human ACE2 transgenic mice, 3Ro-NC + KFDi.n immunization significantly reduces the tissue pathology in the lung and lowers the viral RNA copy numbers in both the lung (85.7-fold) and the nasal turbinate (13.6-fold). Nasal virologic control is highly correlated with RBD-specific secretory IgA antibodies. Our data show that 3Ro-NC plus KFD is a promising mucosal vaccine candidate for protection against SARS-CoV-2 Omicron infection, pathology and transmission potential.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
COVID-19 Vaccines
/
COVID-19
Topics:
Vaccines
/
Variants
Limits:
Animals
/
Humans
Language:
English
Journal:
Cell Mol Immunol
Journal subject:
Allergy and Immunology
Year:
2022
Document Type:
Article
Affiliation country:
S41423-022-00929-3
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