tetano
Editor, Senior Moderator
Signal Transduct Target Ther
. 2024 Apr 27;9(1):114.
doi: 10.1038/s41392-024-01822-3. Nasal vaccination of triple-RBD scaffold protein with flagellin elicits long-term protection against SARS-CoV-2 variants including JN.1
Xian Li[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Mengxin Xu[SUP] #[/SUP][SUP] 4 [/SUP], Jingyi Yang[SUP] #[/SUP][SUP] 5 [/SUP], Li Zhou[SUP] 6 [/SUP], Lin Liu[SUP] 4 [/SUP], Min Li[SUP] 2 [/SUP], Shasha Wang[SUP] 2 [/SUP], Mei-Qin Liu[SUP] 1 [/SUP], Zhixiang Huang[SUP] 6 [/SUP], Zhen Zhang[SUP] 6 [/SUP], Shuning Liu[SUP] 4 [/SUP], Yunqi Hu[SUP] 4 [/SUP], Haofeng Lin[SUP] 1 3 [/SUP], Bowen Liu[SUP] 1 2 3 [/SUP], Ying Sun[SUP] 7 [/SUP], Qingguo Wu[SUP] 2 [/SUP], Zheng-Li Shi[SUP] 1 [/SUP], Ke Lan[SUP] 6 [/SUP], Yu Chen[SUP] 8 [/SUP], Huimin Yan[SUP] 9 10 11 [/SUP], Yao-Qing Chen[SUP] 12 13 [/SUP]
Affiliations
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.
. 2024 Apr 27;9(1):114.
doi: 10.1038/s41392-024-01822-3. Nasal vaccination of triple-RBD scaffold protein with flagellin elicits long-term protection against SARS-CoV-2 variants including JN.1
Xian Li[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Mengxin Xu[SUP] #[/SUP][SUP] 4 [/SUP], Jingyi Yang[SUP] #[/SUP][SUP] 5 [/SUP], Li Zhou[SUP] 6 [/SUP], Lin Liu[SUP] 4 [/SUP], Min Li[SUP] 2 [/SUP], Shasha Wang[SUP] 2 [/SUP], Mei-Qin Liu[SUP] 1 [/SUP], Zhixiang Huang[SUP] 6 [/SUP], Zhen Zhang[SUP] 6 [/SUP], Shuning Liu[SUP] 4 [/SUP], Yunqi Hu[SUP] 4 [/SUP], Haofeng Lin[SUP] 1 3 [/SUP], Bowen Liu[SUP] 1 2 3 [/SUP], Ying Sun[SUP] 7 [/SUP], Qingguo Wu[SUP] 2 [/SUP], Zheng-Li Shi[SUP] 1 [/SUP], Ke Lan[SUP] 6 [/SUP], Yu Chen[SUP] 8 [/SUP], Huimin Yan[SUP] 9 10 11 [/SUP], Yao-Qing Chen[SUP] 12 13 [/SUP]
Affiliations
- PMID: 38678055
- PMCID: PMC11055866
- DOI: 10.1038/s41392-024-01822-3
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.