An RBD-Fc mucosal vaccine provides variant-proof protection against SARS-CoV-2 in mice and hamsters
Abstract Current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are effective against severe disease and death, but do not prevent viral infections, probably due to the limited mucosal immunity induced by intramuscular administration of the vaccine. Fusion of SARS-CoV-2 subuni...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-05-01
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| Series: | npj Vaccines |
| Online Access: | https://doi.org/10.1038/s41541-025-01155-4 |
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| author | Yanjun Zhang Yan Wu Meng-Qian Zhang Haiyue Rao Zhaoyong Zhang Xiangyue He Yiwen Liang Raoqing Guo Yaochang Yuan Jing Sun Helen M. E. Duyvesteyn Elizabeth E. Fry David I. Stuart Jingxian Zhao XiaoYan Pan Shu-Lin Liu Jincun Zhao Jiandong Huo |
| author_facet | Yanjun Zhang Yan Wu Meng-Qian Zhang Haiyue Rao Zhaoyong Zhang Xiangyue He Yiwen Liang Raoqing Guo Yaochang Yuan Jing Sun Helen M. E. Duyvesteyn Elizabeth E. Fry David I. Stuart Jingxian Zhao XiaoYan Pan Shu-Lin Liu Jincun Zhao Jiandong Huo |
| author_sort | Yanjun Zhang |
| collection | DOAJ |
| description | Abstract Current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are effective against severe disease and death, but do not prevent viral infections, probably due to the limited mucosal immunity induced by intramuscular administration of the vaccine. Fusion of SARS-CoV-2 subunit immunogens with a human IgG Fc backbone can be used as a mucosal vaccine but its effectiveness in delivery in animal models, and its immunogenicity and the vaccine-induced protection against viral infections requires further studies. Here we investigate a bivalent RBD-Fc vaccine that includes the spike receptor-binding domains (RBDs) of the ancestral and BQ.1.1 variant of SARS-CoV-2. Ex vivo fluorescent imaging demonstrates that this vaccine can be effectively delivered to the lungs of mice through intranasal administration, with enhancement of retention in the nasal cavity and lung parenchyma. In mice, the vaccine elicited potent and broad-spectrum antibody responses against different variants including KP.3 which could persist for at least 3 months after booster. Importantly, it was able to induce RBD-specific mucosal IgA responses. Further, heterologous intranasal immunisation with adeno-vectored Chadv1 and RBD-Fc elicited both potent neutralising antibody and T cell responses. Immunised BALB/c and K18-hACE2-transgenic mice were also protected against viral challenge of XBB.1 and viral transmission was effectively limited in hamsters through intranasal immunisation. This work thus demonstrates the potential of RBD-Fc antigens as mucosal vaccines for prevention of breakthrough infections and onward transmission. Moreover, Fc-fusion proteins can be used as an effective mucosal vaccine strategy which can be used either alone or in combination with other vaccine technology to constitute heterologous immunisations, enabling strong protection against SARS-CoV-2 and other respiratory viruses. |
| format | Article |
| id | doaj-art-050e2bb346fb422fac6e07b5115166d8 |
| institution | Kabale University |
| issn | 2059-0105 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Vaccines |
| spelling | doaj-art-050e2bb346fb422fac6e07b5115166d82025-08-20T03:45:44ZengNature Portfolionpj Vaccines2059-01052025-05-0110111310.1038/s41541-025-01155-4An RBD-Fc mucosal vaccine provides variant-proof protection against SARS-CoV-2 in mice and hamstersYanjun Zhang0Yan Wu1Meng-Qian Zhang2Haiyue Rao3Zhaoyong Zhang4Xiangyue He5Yiwen Liang6Raoqing Guo7Yaochang Yuan8Jing Sun9Helen M. E. Duyvesteyn10Elizabeth E. Fry11David I. Stuart12Jingxian Zhao13XiaoYan Pan14Shu-Lin Liu15Jincun Zhao16Jiandong Huo17State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical UniversityState Key Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Chinese Academy of SciencesState Key Laboratory of Medicinal Chemical Biology, TianjinKey Laboratory of Biosensing and Molecular Recognition,Frontiers Science Centre for New Organic Matter, ResearchCentre for Analytical Sciences, College of Chemistry, Nankai UniversityState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical UniversityState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical UniversityState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical UniversityState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical UniversityState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical UniversityState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical UniversityState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical UniversityDivision of Structural Biology, Nuffield Department of Medicine, University of Oxford, The Wellcome Centre for Human GeneticsDivision of Structural Biology, Nuffield Department of Medicine, University of Oxford, The Wellcome Centre for Human GeneticsDivision of Structural Biology, Nuffield Department of Medicine, University of Oxford, The Wellcome Centre for Human GeneticsState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical UniversityState Key Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Chinese Academy of SciencesState Key Laboratory of Medicinal Chemical Biology, TianjinKey Laboratory of Biosensing and Molecular Recognition,Frontiers Science Centre for New Organic Matter, ResearchCentre for Analytical Sciences, College of Chemistry, Nankai UniversityState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical UniversityState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical UniversityAbstract Current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are effective against severe disease and death, but do not prevent viral infections, probably due to the limited mucosal immunity induced by intramuscular administration of the vaccine. Fusion of SARS-CoV-2 subunit immunogens with a human IgG Fc backbone can be used as a mucosal vaccine but its effectiveness in delivery in animal models, and its immunogenicity and the vaccine-induced protection against viral infections requires further studies. Here we investigate a bivalent RBD-Fc vaccine that includes the spike receptor-binding domains (RBDs) of the ancestral and BQ.1.1 variant of SARS-CoV-2. Ex vivo fluorescent imaging demonstrates that this vaccine can be effectively delivered to the lungs of mice through intranasal administration, with enhancement of retention in the nasal cavity and lung parenchyma. In mice, the vaccine elicited potent and broad-spectrum antibody responses against different variants including KP.3 which could persist for at least 3 months after booster. Importantly, it was able to induce RBD-specific mucosal IgA responses. Further, heterologous intranasal immunisation with adeno-vectored Chadv1 and RBD-Fc elicited both potent neutralising antibody and T cell responses. Immunised BALB/c and K18-hACE2-transgenic mice were also protected against viral challenge of XBB.1 and viral transmission was effectively limited in hamsters through intranasal immunisation. This work thus demonstrates the potential of RBD-Fc antigens as mucosal vaccines for prevention of breakthrough infections and onward transmission. Moreover, Fc-fusion proteins can be used as an effective mucosal vaccine strategy which can be used either alone or in combination with other vaccine technology to constitute heterologous immunisations, enabling strong protection against SARS-CoV-2 and other respiratory viruses.https://doi.org/10.1038/s41541-025-01155-4 |
| spellingShingle | Yanjun Zhang Yan Wu Meng-Qian Zhang Haiyue Rao Zhaoyong Zhang Xiangyue He Yiwen Liang Raoqing Guo Yaochang Yuan Jing Sun Helen M. E. Duyvesteyn Elizabeth E. Fry David I. Stuart Jingxian Zhao XiaoYan Pan Shu-Lin Liu Jincun Zhao Jiandong Huo An RBD-Fc mucosal vaccine provides variant-proof protection against SARS-CoV-2 in mice and hamsters npj Vaccines |
| title | An RBD-Fc mucosal vaccine provides variant-proof protection against SARS-CoV-2 in mice and hamsters |
| title_full | An RBD-Fc mucosal vaccine provides variant-proof protection against SARS-CoV-2 in mice and hamsters |
| title_fullStr | An RBD-Fc mucosal vaccine provides variant-proof protection against SARS-CoV-2 in mice and hamsters |
| title_full_unstemmed | An RBD-Fc mucosal vaccine provides variant-proof protection against SARS-CoV-2 in mice and hamsters |
| title_short | An RBD-Fc mucosal vaccine provides variant-proof protection against SARS-CoV-2 in mice and hamsters |
| title_sort | rbd fc mucosal vaccine provides variant proof protection against sars cov 2 in mice and hamsters |
| url | https://doi.org/10.1038/s41541-025-01155-4 |
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