Volume 9 Issue 12, Dec 2024

ISSN: 2095-9907 

EISSN: 2059-23635 

2023 impact factor 40.8 

 (Clarivate Analytics, 2024)
Volume 9 Issue 12, Dec 2024:
Article
Intranasal delivery of a subunit protein vaccine provides protective immunity against JN.1 and XBB-lineage variants
Hong Lei,Weiqi Hong ORCID: orcid.org/0000-0003-1668-2301,Jingyun Yang,Cai He,Yanan Zhou,Yu Zhang,Aqu Alu ORCID: orcid.org/0000-0002-9981-0120,Jie Shi,Jian Liu,Furong qin,Danyi Ao,Xiya Huang,Zimin Chen ORCID: orcid.org/0000-0002-2862-9674,Hao Yang,Yun Yang,Wenhai Yu,Cong Tang,Junbin Wang,Bai Li,Qing Huang,Hongbo Hu ORCID: orcid.org/0000-0002-8177-7641,Wei Cheng,Haohao Dong ORCID: orcid.org/0000-0002-5022-3494,Jian Lei ORCID: orcid.org/0000-0001-9326-0554,Lu Chen ORCID: orcid.org/0000-0002-1083-9729,Xikun Zhou ORCID: orcid.org/0000-0001-6768-2382,Jiong Li ORCID: orcid.org/0000-0002-3742-630X,Li Yang,Zhenling Wang,Wei Wang ORCID: orcid.org/0000-0001-7788-1895,Guobo Shen ORCID: orcid.org/0000-0002-8917-196X,Jinliang Yang,Zhiwei Zhao,Xiangrong Song ORCID: orcid.org/0000-0002-2853-2696,Guangwen Lu ORCID: orcid.org/0000-0001-7568-592X,Qiangming Sun,Youchun Wang,Shuaiyao Lu ORCID: orcid.org/0000-0003-1675-9735 &…Xiawei Wei ORCID: orcid.org/0000-0002-6513-6422
The mucosal immune response plays a crucial role in the prevention of respiratory viruses. Given the risk of recurrent SARS-CoV-2 infections in the population, the rapid development of next-generation intranasal COVID-19 vaccines with high safety and efficacy is paramount. In the current study, we developed a protein-based intranasal vaccine comprising the XBB.1.5 receptor binding domain (RBD)-derived trimeric recombinant protein (RBDXBB.1.5-HR) and an MF59-like oil-in-water adjuvant. Intranasal administration of RBDXBB.1.5-HR vaccine elicited robust and sustained humoral immune responses in mice and rats, resulting in high levels of neutralizing antibodies against XBB-lineage subvariants, with protection lasting for at least six months. The intranasal RBDXBB.1.5-HR vaccine generated potent mucosal immune responses, characterized by the inductions of tissue-resident T (TRM) cells, local cellular immunity, germinal center, and memory B cell responses in the respiratory tract. The combination of intramuscular and intranasal delivery of the RBDXBB.1.5-HR vaccine demonstrated exceptional systemic and mucosal protective immunity. Furthermore, intranasal delivery of RBDXBB.1.5-HR vaccine as a heterologous booster shot showed more effective boosting effects after mRNA administration compared to homologous vaccination, as evidenced by the induction of superior systemic and extra mucosal immune response. Importantly, the intranasal RBDXBB.1.5-HR vaccine conferred efficient protection against the challenge with authentic EG.5.1 viruses in vivo. These findings identify the intranasal RBDXBB.1.5-HR vaccine as a potential mucosal vaccine candidate for the prevention of SARS-CoV-2 infection.