Single-Dose Intranasal Immunisation with Novel Chimeric H1N1 Expressing the Receptor-Binding Domain of SARS-CoV-2 Induces Robust Mucosal Immunity, Tissue-Resident Memory T Cells, and Heterologous Protection in Mice
Current COVID-19 vaccines can effectively reduce disease severity and hospitalisation; however, they are not considerably effective in preventing infection and transmission. In this context, mucosal vaccines are pertinent to prevent SARS-CoV-2 infection and spread. In this study, we generated a repl...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-09-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/11/9/1453 |
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| author | Donghong Wang Yao Deng Jianfang Zhou Wen Wang Baoying Huang Wenling Wang Lan Wei Jiao Ren Ruiwen Han Jialuo Bing Chengcheng Zhai Xiaoyan Guo Wenjie Tan |
| author_facet | Donghong Wang Yao Deng Jianfang Zhou Wen Wang Baoying Huang Wenling Wang Lan Wei Jiao Ren Ruiwen Han Jialuo Bing Chengcheng Zhai Xiaoyan Guo Wenjie Tan |
| author_sort | Donghong Wang |
| collection | DOAJ |
| description | Current COVID-19 vaccines can effectively reduce disease severity and hospitalisation; however, they are not considerably effective in preventing infection and transmission. In this context, mucosal vaccines are pertinent to prevent SARS-CoV-2 infection and spread. In this study, we generated a replication-competent recombinant chimeric influenza A virus (IAV) expressing the receptor-binding domain (RBD) of a SARS-CoV-2 prototype in the C-terminus of the neuraminidase (NA) of A/Puerto Rico/08/1934 H1N1 (PR8). The remaining seven segments from A/WSN/1933 H1N1 (WSN) were named PR8NARBD/WSN. We observed that the recombinant virus with the WSN backbone demonstrated improved expression of NA and RBD. A single intranasal dose of PR8NARBD/WSN(10<sup>3</sup>PFU) in mice generated robust mucosal immunity, neutralising antibodies, cellular immunity, and tissue-resident memory T cells specific to SARS-CoV-2 and IAV. Importantly, immunisation with PR8NARBD/WSN viruses effectively protected mice against lethal challenges with H1N1, H3N2 IAV, and SARS-CoV-2 Beta variant and significantly reduced lung viral loads. Overall, our research demonstrates the promising potential of PR8NARBD/WSN as an attractive vaccine against emerging SARS-CoV-2 variants and influenza A virus infections. |
| first_indexed | 2024-03-10T21:52:14Z |
| format | Article |
| id | doaj.art-1ee59533be7c4629b5e0e984a2a1bb07 |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-10T21:52:14Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-1ee59533be7c4629b5e0e984a2a1bb072023-11-19T13:19:10ZengMDPI AGVaccines2076-393X2023-09-01119145310.3390/vaccines11091453Single-Dose Intranasal Immunisation with Novel Chimeric H1N1 Expressing the Receptor-Binding Domain of SARS-CoV-2 Induces Robust Mucosal Immunity, Tissue-Resident Memory T Cells, and Heterologous Protection in MiceDonghong Wang0Yao Deng1Jianfang Zhou2Wen Wang3Baoying Huang4Wenling Wang5Lan Wei6Jiao Ren7Ruiwen Han8Jialuo Bing9Chengcheng Zhai10Xiaoyan Guo11Wenjie Tan12Key Laboratory of Biosafety, National Health Commissions, National Institute for Viral Disease Control and Prevention, China CDC, 155 Changbai Road, Beijing 102206, ChinaKey Laboratory of Biosafety, National Health Commissions, National Institute for Viral Disease Control and Prevention, China CDC, 155 Changbai Road, Beijing 102206, ChinaState Key Laboratory for Molecular Virology and Genetic Engineering, Chinese National Influenza Center, National Institute for Viral Disease Control and Prevention, China CDC, 155 Changbai Road, Beijing 102206, ChinaKey Laboratory of Biosafety, National Health Commissions, National Institute for Viral Disease Control and Prevention, China CDC, 155 Changbai Road, Beijing 102206, ChinaKey Laboratory of Biosafety, National Health Commissions, National Institute for Viral Disease Control and Prevention, China CDC, 155 Changbai Road, Beijing 102206, ChinaKey Laboratory of Biosafety, National Health Commissions, National Institute for Viral Disease Control and Prevention, China CDC, 155 Changbai Road, Beijing 102206, ChinaKey Laboratory of Biosafety, National Health Commissions, National Institute for Viral Disease Control and Prevention, China CDC, 155 Changbai Road, Beijing 102206, ChinaKey Laboratory of Biosafety, National Health Commissions, National Institute for Viral Disease Control and Prevention, China CDC, 155 Changbai Road, Beijing 102206, ChinaKey Laboratory of Biosafety, National Health Commissions, National Institute for Viral Disease Control and Prevention, China CDC, 155 Changbai Road, Beijing 102206, ChinaKey Laboratory of Biosafety, National Health Commissions, National Institute for Viral Disease Control and Prevention, China CDC, 155 Changbai Road, Beijing 102206, ChinaKey Laboratory of Biosafety, National Health Commissions, National Institute for Viral Disease Control and Prevention, China CDC, 155 Changbai Road, Beijing 102206, ChinaKey Laboratory of Biosafety, National Health Commissions, National Institute for Viral Disease Control and Prevention, China CDC, 155 Changbai Road, Beijing 102206, ChinaKey Laboratory of Biosafety, National Health Commissions, National Institute for Viral Disease Control and Prevention, China CDC, 155 Changbai Road, Beijing 102206, ChinaCurrent COVID-19 vaccines can effectively reduce disease severity and hospitalisation; however, they are not considerably effective in preventing infection and transmission. In this context, mucosal vaccines are pertinent to prevent SARS-CoV-2 infection and spread. In this study, we generated a replication-competent recombinant chimeric influenza A virus (IAV) expressing the receptor-binding domain (RBD) of a SARS-CoV-2 prototype in the C-terminus of the neuraminidase (NA) of A/Puerto Rico/08/1934 H1N1 (PR8). The remaining seven segments from A/WSN/1933 H1N1 (WSN) were named PR8NARBD/WSN. We observed that the recombinant virus with the WSN backbone demonstrated improved expression of NA and RBD. A single intranasal dose of PR8NARBD/WSN(10<sup>3</sup>PFU) in mice generated robust mucosal immunity, neutralising antibodies, cellular immunity, and tissue-resident memory T cells specific to SARS-CoV-2 and IAV. Importantly, immunisation with PR8NARBD/WSN viruses effectively protected mice against lethal challenges with H1N1, H3N2 IAV, and SARS-CoV-2 Beta variant and significantly reduced lung viral loads. Overall, our research demonstrates the promising potential of PR8NARBD/WSN as an attractive vaccine against emerging SARS-CoV-2 variants and influenza A virus infections.https://www.mdpi.com/2076-393X/11/9/1453COVID-19influenza virusheterologous protectionrecombinant vaccineT cell immunity |
| spellingShingle | Donghong Wang Yao Deng Jianfang Zhou Wen Wang Baoying Huang Wenling Wang Lan Wei Jiao Ren Ruiwen Han Jialuo Bing Chengcheng Zhai Xiaoyan Guo Wenjie Tan Single-Dose Intranasal Immunisation with Novel Chimeric H1N1 Expressing the Receptor-Binding Domain of SARS-CoV-2 Induces Robust Mucosal Immunity, Tissue-Resident Memory T Cells, and Heterologous Protection in Mice Vaccines COVID-19 influenza virus heterologous protection recombinant vaccine T cell immunity |
| title | Single-Dose Intranasal Immunisation with Novel Chimeric H1N1 Expressing the Receptor-Binding Domain of SARS-CoV-2 Induces Robust Mucosal Immunity, Tissue-Resident Memory T Cells, and Heterologous Protection in Mice |
| title_full | Single-Dose Intranasal Immunisation with Novel Chimeric H1N1 Expressing the Receptor-Binding Domain of SARS-CoV-2 Induces Robust Mucosal Immunity, Tissue-Resident Memory T Cells, and Heterologous Protection in Mice |
| title_fullStr | Single-Dose Intranasal Immunisation with Novel Chimeric H1N1 Expressing the Receptor-Binding Domain of SARS-CoV-2 Induces Robust Mucosal Immunity, Tissue-Resident Memory T Cells, and Heterologous Protection in Mice |
| title_full_unstemmed | Single-Dose Intranasal Immunisation with Novel Chimeric H1N1 Expressing the Receptor-Binding Domain of SARS-CoV-2 Induces Robust Mucosal Immunity, Tissue-Resident Memory T Cells, and Heterologous Protection in Mice |
| title_short | Single-Dose Intranasal Immunisation with Novel Chimeric H1N1 Expressing the Receptor-Binding Domain of SARS-CoV-2 Induces Robust Mucosal Immunity, Tissue-Resident Memory T Cells, and Heterologous Protection in Mice |
| title_sort | single dose intranasal immunisation with novel chimeric h1n1 expressing the receptor binding domain of sars cov 2 induces robust mucosal immunity tissue resident memory t cells and heterologous protection in mice |
| topic | COVID-19 influenza virus heterologous protection recombinant vaccine T cell immunity |
| url | https://www.mdpi.com/2076-393X/11/9/1453 |
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