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Journal Article Ppublish 104 citations

PubMed: 35637645 DOI: 10.1016/j.scib.2022.05.018

A live attenuated virus-based intranasal COVID-19 vaccine provides rapid, prolonged, and broad protection against SARS-CoV-2.

Sci Bull (Beijing) 67(13):1372-1387

Authors: Junyu Chen, Pui Wang, Lunzhi Yuan, Liang Zhang, Limin Zhang, Hui Zhao, Congjie Chen, Xijing Wang, Jinle Han, Yaode Chen, Jizong Jia, Zhen Lu, Junping Hong, Zicen Lu, Qian Wang, Rirong Chen, Ruoyao Qi, Jian Ma, Min Zhou, Huan Yu, Chunlan Zhuang, Xiaohui Liu, Qiangyuan Han, Guosong Wang, Yingying Su, Quan Yuan, Tong Cheng, Ting Wu, Xiangzhong Ye, Tianying Zhang, Changgui Li, Jun Zhang, Huachen Zhu, Yixin Chen, Honglin Chen, Ningshao Xia

Affiliations

  • State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, School of Public Health, Xiamen University, Xiamen 361102, China.
  • State Key Laboratory of Emerging Infectious Diseases, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong 999077, China.
  • National Institute for Food and Drug Control, Beijing 102629, China.
  • Beijing Wantai Biological Pharmacy Enterprise Co. Ltd. Beijing 102206, China.
  • Guangdong-Hong Kong Joint Laboratory of Emerging Infectious Diseases/Joint Laboratory for International Collaboration in Virology and Emerging Infectious Diseases, Joint Institute of Virology (STU/HKU), Shantou University, Shantou 515063, China.
  • EKIH Pathogen Research Institute, Shenzhen 518067, China.

Abstract

Remarkable progress has been made in developing intramuscular vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); however, they are limited with respect to eliciting local immunity in the respiratory tract, which is the primary infection site for SARS-CoV-2. To overcome the limitations of intramuscular vaccines, we constructed a nasal vaccine candidate based on an influenza vector by inserting a gene encoding the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2, named CA4-dNS1-nCoV-RBD (dNS1-RBD). A preclinical study showed that in hamsters challenged 1 d after single-dose vaccination or 9 months after booster vaccination, dNS1-RBD largely mitigated lung pathology, with no loss of body weight. Moreover, such cellular immunity is relatively unimpaired for the most concerning SARS-CoV-2 variants, especially for the latest Omicron variant. In addition, this vaccine also provides cross-protection against H1N1 and H5N1 influenza viruses. The protective immune mechanism of dNS1-RBD could be attributed to the innate immune response in the nasal epithelium, local RBD-specific T cell response in the lung, and RBD-specific IgA and IgG response. Thus, this study demonstrates that the intranasally delivered dNS1-RBD vaccine candidate may offer an important addition to the fight against the ongoing coronavirus disease 2019 pandemic and influenza infection, compensating limitations of current intramuscular vaccines.

MeSH

Cells, Coronavirus, Sars-Cov-2, Lung, Vaccines, Covid-19 Vaccines, Vaccination, Covid-19, Influenza, Human, Viruses, Immunity, Severe Acute Respiratory Syndrome-Related Coronavirus, Infections

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