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: Flagellin adjuvant; Intranasal immunization; Mucosal vaccine; SARS-CoV-2; Triple-RBD; Variant of concern.
【저자키워드】 SARS-CoV-2, Variant of concern., mucosal vaccine, intranasal immunization, Triple-RBD, Flagellin adjuvant, 【초록키워드】 neutralizing antibody, antibodies, pathology, Vaccine, Mutation, variant, SARS-CoV-2 variant, Infection, Delta, lung, nasal, omicron, immunization, human ACE2, Spread, Protein, specificity, RBD, IgA, transmission potential, vaccine candidate, Viral RNA, intranasal, mucosal, secretory IgA, chimeric, flagellin, antigenic, transgenic mice, Lower, effective, neutralizing immunity, initial, tissue pathology, significantly, correlated, elicit, reduce, 【제목키워드】 Vaccine, SARS-CoV-2 variant, mucosal, provide,