Intranasal delivery of a subunit protein vaccine provides protective immunity against JN.1 and XBB-lineage variants

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 (RBD<sub>XBB.1.5</sub>-HR) and an MF59-like oil-in-water adjuvant. Intranasal administration of RBD<sub>XBB.1.5</sub>-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 RBD<sub>XBB.1.5</sub>-HR vaccine generated potent mucosal immune responses, characterized by the inductions of tissue-resident T (T<sub>RM</sub>) cells, local cellular immunity, germinal center, and memory B cell responses in the respiratory tract. The combination of intramuscular and intranasal delivery of the RBD<sub>XBB.1.5</sub>-HR vaccine demonstrated exceptional systemic and mucosal protective immunity. Furthermore, intranasal delivery of RBD<sub>XBB.1.5</sub>-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 RBD<sub>XBB.1.5</sub>-HR vaccine conferred efficient protection against the challenge with authentic EG.5.1 viruses in vivo. These findings identify the intranasal RBD<sub>XBB.1.5</sub>-HR vaccine as a potential mucosal vaccine candidate for the prevention of SARS-CoV-2 infection.

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Publication Details

Journal
Signal Transduction and Targeted Therapy
Published
2024-11-20
DOI
https://doi.org/10.1038/s41392-024-02025-6
Citations
11
Primary Topic
SARS-CoV-2 and COVID-19 Research
Type
article
Field-Weighted Citation Impact
4.28

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article

Intranasal delivery of a subunit protein vaccine provides protective immunity against JN.1 and XBB-lineage variants

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11 citations
Signal Transduction and Targeted Therapy
SARS-CoV-2 and COVID-19 Research
4.28
article

Intranasal delivery of a subunit protein vaccine provides protective immunity against JN.1 and XBB-lineage variants

Xiawei Wei, Xiangrong Song, Wei Cheng, Qiangming Sun, Weiqi Hong, Bai Li, Xikun Zhou, Aqu Alu, Zimin Chen, Danyi Ao, Jinliang Yang, Guobo Shen, Haohao Dong, Guangwen Lu, Jian Lei, Hongbo Hu, Shuaiyao Lu, Jiong Li, Wenhai Yu, H. J. Yang, Wei Wang, Lu Chen, Li Yang, Lei Hong, Jie Shi, Jian Liu, Yun Yang, Yanan Zhou, Qing Huang, Zhiwei Zhao, Zhenling Wang, Junbin Wang, Cong Tang, Xiya Huang, Cai He, Yu Zhang, Youchun Wang, Hao Yang
article en
11 citations

Abstract

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 (RBD<sub>XBB.1.5</sub>-HR) and an MF59-like oil-in-water adjuvant. Intranasal administration of RBD<sub>XBB.1.5</sub>-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 RBD<sub>XBB.1.5</sub>-HR vaccine generated potent mucosal immune responses, characterized by the inductions of tissue-resident T (T<sub>RM</sub>) cells, local cellular immunity, germinal center, and memory B cell responses in the respiratory tract. The combination of intramuscular and intranasal delivery of the RBD<sub>XBB.1.5</sub>-HR vaccine demonstrated exceptional systemic and mucosal protective immunity. Furthermore, intranasal delivery of RBD<sub>XBB.1.5</sub>-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 RBD<sub>XBB.1.5</sub>-HR vaccine conferred efficient protection against the challenge with authentic EG.5.1 viruses in vivo. These findings identify the intranasal RBD<sub>XBB.1.5</sub>-HR vaccine as a potential mucosal vaccine candidate for the prevention of SARS-CoV-2 infection.

Signal Transduction and Targeted TherapyVol. 9(1)
Chinese Academy of Medical Sciences & Peking Union Medical College (CN), Sichuan University (CN)
National Science Foundation, National Natural Science Foundation of China, Department of Science and Technology of Sichuan Province
Good health and well-being
Openalex Percentile: Top 5%
SARS-CoV-2 and COVID-19 Research
4.28
DOIOpen Access PDFOpenAlex
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