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

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

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

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 YuChunlan 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

Research output: Contribution to journal › Article › peer-review

82 Scopus citations

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.

Original language	English
Pages (from-to)	1372-1387
Number of pages	16
Journal	Science Bulletin
Volume	67
Issue number	13
DOIs	https://doi.org/10.1016/j.scib.2022.05.018
State	Published - 15 Jul 2022
Externally published	Yes

Keywords

COVID-19
Cell-mediated immunity
Influenza vector
Intranasal vaccine
SARS-CoV-2

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10.1016/j.scib.2022.05.018

Cite this

Chen, J., Wang, P., Yuan, L., Zhang, L., Zhang, L., Zhao, H., Chen, C., Wang, X., Han, J., Chen, Y., Jia, J., Lu, Z., Hong, J., Lu, Z., Wang, Q., Chen, R., Qi, R., Ma, J., Zhou, M., ... Xia, N. (2022). A live attenuated virus-based intranasal COVID-19 vaccine provides rapid, prolonged, and broad protection against SARS-CoV-2. Science Bulletin, 67(13), 1372-1387. https://doi.org/10.1016/j.scib.2022.05.018

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

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.",

keywords = "COVID-19, Cell-mediated immunity, Influenza vector, Intranasal vaccine, SARS-CoV-2",

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

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doi = "10.1016/j.scib.2022.05.018",

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Chen, J, Wang, P, Yuan, L, Zhang, L, Zhang, L, Zhao, H, Chen, C, Wang, X, Han, J, Chen, Y, Jia, J, Lu, Z, Hong, J, Lu, Z, Wang, Q, Chen, R, Qi, R, Ma, J, Zhou, M, Yu, H, Zhuang, C, Liu, X, Han, Q, Wang, G, Su, Y, Yuan, Q, Cheng, T, Wu, T, Ye, X, Zhang, T, Li, C, Zhang, J, Zhu, H, Chen, Y, Chen, H & Xia, N 2022, 'A live attenuated virus-based intranasal COVID-19 vaccine provides rapid, prolonged, and broad protection against SARS-CoV-2', Science Bulletin, vol. 67, no. 13, pp. 1372-1387. https://doi.org/10.1016/j.scib.2022.05.018

TY - JOUR

T1 - A live attenuated virus-based intranasal COVID-19 vaccine provides rapid, prolonged, and broad protection against SARS-CoV-2

AU - Chen, Junyu

AU - Wang, Pui

AU - Yuan, Lunzhi

AU - Zhang, Liang

AU - Zhang, Limin

AU - Zhao, Hui

AU - Chen, Congjie

AU - Wang, Xijing

AU - Han, Jinle

AU - Chen, Yaode

AU - Jia, Jizong

AU - Lu, Zhen

AU - Hong, Junping

AU - Lu, Zicen

AU - Wang, Qian

AU - Chen, Rirong

AU - Qi, Ruoyao

AU - Ma, Jian

AU - Zhou, Min

AU - Yu, Huan

AU - Zhuang, Chunlan

AU - Liu, Xiaohui

AU - Han, Qiangyuan

AU - Wang, Guosong

AU - Su, Yingying

AU - Yuan, Quan

AU - Cheng, Tong

AU - Wu, Ting

AU - Ye, Xiangzhong

AU - Zhang, Tianying

AU - Li, Changgui

AU - Zhang, Jun

AU - Zhu, Huachen

AU - Chen, Yixin

AU - Chen, Honglin

AU - Xia, Ningshao

PY - 2022/7/15

Y1 - 2022/7/15

N2 - 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.

AB - 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.

KW - COVID-19

KW - Cell-mediated immunity

KW - Influenza vector

KW - Intranasal vaccine

KW - SARS-CoV-2

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U2 - 10.1016/j.scib.2022.05.018

DO - 10.1016/j.scib.2022.05.018

M3 - Article

AN - SCOPUS:85132921104

SN - 2095-9273

VL - 67

SP - 1372

EP - 1387

JO - Science Bulletin

JF - Science Bulletin

IS - 13

ER -

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

Abstract

Keywords

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