Volume 9 Issue 5, May 2024:
Article
Nasal vaccination of triple-RBD scaffold protein with flagellin elicits long-term protection against SARS-CoV-2 variants including JN.1
Xian Li,Mengxin Xu,Jingyi Yang,Li Zhou,Lin Liu,Min Li,Shasha Wang,Mei-Qin Liu,Zhixiang Huang,Zhen Zhang,Shuning Liu,Yunqi Hu,Haofeng Lin,Bowen Liu,Ying Sun,Qingguo Wu,Zheng-Li Shi
ORCID: orcid.org/0000-0001-8089-163X,Ke Lan
ORCID: orcid.org/0000-0002-0384-8598,Yu Chen
ORCID: orcid.org/0000-0003-1300-4652,Huimin Yan
ORCID: orcid.org/0000-0002-7243-8429 &…Yao-Qing Chen
ORCID: orcid.org/0000-0002-4659-1550
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.
