4.7 Article

A triple-RBD-based mucosal vaccine provides broad protection against SARS-CoV-2 variants of concern

期刊

CELLULAR & MOLECULAR IMMUNOLOGY
卷 19, 期 11, 页码 1279-1289

出版社

CHIN SOCIETY IMMUNOLOGY
DOI: 10.1038/s41423-022-00929-3

关键词

SARS-CoV-2; Mucosal vaccine; Intranasal immunization; Triple-RBD; Flagellin adjuvant; Variant of concern

资金

  1. National Key R&D Program of China [2021YFC2302602]
  2. Chinese Academy of Sciences [XDB29010101, 2020YJFK-Z-0149]
  3. National Natural Science Foundation of China [31970878, 92169104, 31970881]
  4. Shenzhen Science and Technology Program [RCJC20210706092009004, JCYJ20190807154603596]

向作者/读者索取更多资源

This study presents a chimeric immunogen that can induce effective immune responses against SARS-CoV-2 variants. Intranasal immunization with this vaccine generates mucosal immune responses and higher neutralizing antibody specificity against the Omicron variant. In mouse experiments, it is found that vaccination with this candidate can reduce lung pathology and decrease viral RNA copy numbers. Nasal virologic control is closely associated with RBD-specific secretory IgA antibodies.
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.

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