A live attenuated influenza virus-vectored intranasal COVID-19 vaccine provides rapid, prolonged, and broad protection against SARS-CoV-2 infection
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 day and 7 days after single-dose vaccination or 6 months after booster vaccination, dNS1-RBD largely mitigated lung pathology, with no loss of body weight, caused by either the prototype-like strain or beta variant of SARS-CoV-2. Lasted data showed that the animals could be well protected against beta variant challenge 9 months after vaccination. Notably, the weight loss and lung pathological changes of hamsters could still be significantly reduced when the hamster was vaccinated 24 h after challenge. Moreover, such cellular immunity is relatively unimpaired for the most concerning SARS-CoV-2 variants. 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 fight against the ongoing COVID-19 pandemic, compensating limitations of current intramuscular vaccines, particularly at the start of an outbreak..
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Preprint| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
bioRxiv.org - (2022) vom: 28. Okt. Zur Gesamtaufnahme - year:2022 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Chen, Junyu [VerfasserIn] |
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| doi: |
10.1101/2021.11.13.468472 |
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| PPN (Katalog-ID): |
XBI033028729 |
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| 245 | 1 | 0 | |a A live attenuated influenza virus-vectored intranasal COVID-19 vaccine provides rapid, prolonged, and broad protection against SARS-CoV-2 infection |
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| 520 | |a 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 day and 7 days after single-dose vaccination or 6 months after booster vaccination, dNS1-RBD largely mitigated lung pathology, with no loss of body weight, caused by either the prototype-like strain or beta variant of SARS-CoV-2. Lasted data showed that the animals could be well protected against beta variant challenge 9 months after vaccination. Notably, the weight loss and lung pathological changes of hamsters could still be significantly reduced when the hamster was vaccinated 24 h after challenge. Moreover, such cellular immunity is relatively unimpaired for the most concerning SARS-CoV-2 variants. 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 fight against the ongoing COVID-19 pandemic, compensating limitations of current intramuscular vaccines, particularly at the start of an outbreak. | ||
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| 700 | 1 | |a Wang, Pui |e verfasserin |4 aut | |
| 700 | 1 | |a Yuan, Lunzhi |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Liang |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Limin |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Hui |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Congjie |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Yaode |e verfasserin |4 aut | |
| 700 | 1 | |a Han, Jinle |e verfasserin |4 aut | |
| 700 | 1 | |a Jia, Jizong |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Zhen |e verfasserin |4 aut | |
| 700 | 1 | |a Hong, Junping |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Liqiang |e verfasserin |4 aut | |
| 700 | 1 | |a Fan, Changfa |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Zicen |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Qian |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Rirong |e verfasserin |4 aut | |
| 700 | 1 | |a Cai, Minping |e verfasserin |4 aut | |
| 700 | 1 | |a Qi, Ruoyao |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Xijing |e verfasserin |4 aut | |
| 700 | 1 | |a Ma, Jian |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Min |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Huan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhuang, Chunlan |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Xiaohui |e verfasserin |4 aut | |
| 700 | 1 | |a Han, Qiangyuan |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Guosong |e verfasserin |4 aut | |
| 700 | 1 | |a Su, Yingying |e verfasserin |4 aut | |
| 700 | 1 | |a Yuan, Quan |e verfasserin |4 aut | |
| 700 | 1 | |a Cheng, Tong |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Ting |e verfasserin |4 aut | |
| 700 | 1 | |a Ye, Xiangzhong |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Changgui |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Tianying |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Jun |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Huachen |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Yixin |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Honglin |e verfasserin |4 aut | |
| 700 | 1 | |a Xia, Ningshao |e verfasserin |4 aut | |
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