摘要
Developing a mucosal vaccine against SARS-CoV-2 is critical for combatting the epidemic.Here,we investigated long-term immune responses and protection against SARS-CoV-2 for the intranasal vaccination of a triple receptor-binding domain(RBD)scaffold protein(3R-NC)adjuvanted with a flagellin protein(KFD)(3R-NC+KFDi.n).In mice,the vaccination elicited RBD-specific broad-neutralizing antibody responses in both serum and mucosal sites sustained at high level over a year.This long-lasting humoral immunity was correlated with the presence of long-lived RBD-specific IgG-and IgA-producing plasma cells,alongside the Th17 and Tfh17-biased T-cell responses driven by the KFD adjuvant.Based upon these preclinical findings,an open labeled clinical trial was conducted in individuals who had been primed with the inactivated SARS-CoV-2(IAV)vaccine.With a favorable safety profile,the 3R-NC+KFDi.n boost elicited enduring broad-neutralizing IgG in plasma and IgA in salivary secretions.To meet the challenge of frequently emerged variants,we further designed an updated triple-RBD scaffold protein with mutated RBD combinations,which can induce adaptable antibody responses to neutralize the newly emerging variants,including JN.1.Our findings highlight the potential of the KFD-adjuvanted triple-RBD scaffold protein is a promising prototype for the development of a mucosal vaccine against SARS-CoV-2 infection.
基金
National Key R&D program of China(Grant number:2022YFC2304204 to Y.-Q.C.,2021YFC2302602 to J.Y.)
National Natural Science Foundation of China(grant number:82341041 to H.Y.and 92169104 to Y.-Q.C.)
Shanghai Science and Technology Innovation Action Plan(Grant number:22Y11901000 to Q.W.)
Shenzhen Science and Technology Program(Grant number:RCJC20210706092009004,JCYJ2020010914243811,KQTD20200820145822023 to Y.-Q.C.)supported this work in whole or in part.
