A single vaccination of nucleoside-modified Rabies mRNA vaccine induces prolonged highly protective immune responses in mice
BackgroundRabies is a lethal zoonotic disease that kills approximately 60,000 people each year. Although inactivated rabies vaccines are available, multiple-dose regimensare recommended for pre-exposure prophylaxis or post-exposure prophylaxis,which cuts down the cost- and time-effectiveness, especi...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1099991/full |
| _version_ | 1797943402797465600 |
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| author | Shimeng Bai Tianhan Yang Cuisong Zhu Meiqi Feng Li Zhang Ziling Zhang Xiang Wang Rui Yu Xinghao Pan Chen Zhao Jianqing Xu Jianqing Xu Xiaoyan Zhang Xiaoyan Zhang |
| author_facet | Shimeng Bai Tianhan Yang Cuisong Zhu Meiqi Feng Li Zhang Ziling Zhang Xiang Wang Rui Yu Xinghao Pan Chen Zhao Jianqing Xu Jianqing Xu Xiaoyan Zhang Xiaoyan Zhang |
| author_sort | Shimeng Bai |
| collection | DOAJ |
| description | BackgroundRabies is a lethal zoonotic disease that kills approximately 60,000 people each year. Although inactivated rabies vaccines are available, multiple-dose regimensare recommended for pre-exposure prophylaxis or post-exposure prophylaxis,which cuts down the cost- and time-effectiveness, especially in low- and middle incomecountries.MethodsWe developed a nucleoside-modified Rabies mRNA-lipid nanoparticle vaccine (RABV-G mRNA-LNP) encoding codon-optimized viral glycoprotein and assessed the immunogenicity and protective efficacy of this vaccine in mice comparing to a commercially available inactivated vaccine.ResultsWe first showed that, when evaluated in mice, a single vaccination of RABV-G mRNA with a moderate or high dose induces more potent humoral and T-cell immune responses than that elicited by three inoculations of the inactivated vaccine. Importantly, mice receiving a single immunization of RABV-G mRNA, even at low doses, showed full protection against the lethal rabies challenge. We further demonstrated that the humoral immune response induced by single RABV-G mRNA vaccination in mice could last for at least 25 weeks, while a two-dose strategy could extend the duration of the highly protective response to one year or even longer. In contrast, the three-dose regimen of inactivated vaccine failed to do so.ConclusionOur study confirmed that it is worth developing a single-dose nucleoside-modified Rabies mRNA-LNP vaccine, which could confer much prolonged and more effective protection. |
| first_indexed | 2024-04-10T20:22:33Z |
| format | Article |
| id | doaj.art-da7f89c5a61e4520aa0f8f689d3fc251 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-10T20:22:33Z |
| publishDate | 2023-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-da7f89c5a61e4520aa0f8f689d3fc2512023-01-25T14:49:20ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-01-011310.3389/fimmu.2022.10999911099991A single vaccination of nucleoside-modified Rabies mRNA vaccine induces prolonged highly protective immune responses in miceShimeng Bai0Tianhan Yang1Cuisong Zhu2Meiqi Feng3Li Zhang4Ziling Zhang5Xiang Wang6Rui Yu7Xinghao Pan8Chen Zhao9Jianqing Xu10Jianqing Xu11Xiaoyan Zhang12Xiaoyan Zhang13Shanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Fudan University, Shanghai, ChinaShanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Fudan University, Shanghai, ChinaShanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Fudan University, Shanghai, ChinaShanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Fudan University, Shanghai, ChinaShanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Fudan University, Shanghai, ChinaShanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Fudan University, Shanghai, ChinaShanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Fudan University, Shanghai, ChinaShanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Fudan University, Shanghai, ChinaShanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Fudan University, Shanghai, ChinaShanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Fudan University, Shanghai, ChinaShanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Fudan University, Shanghai, ChinaClinical Center of Biotherapy, Zhongshan Hospital, Fudan University, Shanghai, ChinaShanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Fudan University, Shanghai, ChinaClinical Center of Biotherapy, Zhongshan Hospital, Fudan University, Shanghai, ChinaBackgroundRabies is a lethal zoonotic disease that kills approximately 60,000 people each year. Although inactivated rabies vaccines are available, multiple-dose regimensare recommended for pre-exposure prophylaxis or post-exposure prophylaxis,which cuts down the cost- and time-effectiveness, especially in low- and middle incomecountries.MethodsWe developed a nucleoside-modified Rabies mRNA-lipid nanoparticle vaccine (RABV-G mRNA-LNP) encoding codon-optimized viral glycoprotein and assessed the immunogenicity and protective efficacy of this vaccine in mice comparing to a commercially available inactivated vaccine.ResultsWe first showed that, when evaluated in mice, a single vaccination of RABV-G mRNA with a moderate or high dose induces more potent humoral and T-cell immune responses than that elicited by three inoculations of the inactivated vaccine. Importantly, mice receiving a single immunization of RABV-G mRNA, even at low doses, showed full protection against the lethal rabies challenge. We further demonstrated that the humoral immune response induced by single RABV-G mRNA vaccination in mice could last for at least 25 weeks, while a two-dose strategy could extend the duration of the highly protective response to one year or even longer. In contrast, the three-dose regimen of inactivated vaccine failed to do so.ConclusionOur study confirmed that it is worth developing a single-dose nucleoside-modified Rabies mRNA-LNP vaccine, which could confer much prolonged and more effective protection.https://www.frontiersin.org/articles/10.3389/fimmu.2022.1099991/fullrabiesmRNA vaccinerabies virus glycoproteinvirus-neutralizing antibodieschallenge model |
| spellingShingle | Shimeng Bai Tianhan Yang Cuisong Zhu Meiqi Feng Li Zhang Ziling Zhang Xiang Wang Rui Yu Xinghao Pan Chen Zhao Jianqing Xu Jianqing Xu Xiaoyan Zhang Xiaoyan Zhang A single vaccination of nucleoside-modified Rabies mRNA vaccine induces prolonged highly protective immune responses in mice Frontiers in Immunology rabies mRNA vaccine rabies virus glycoprotein virus-neutralizing antibodies challenge model |
| title | A single vaccination of nucleoside-modified Rabies mRNA vaccine induces prolonged highly protective immune responses in mice |
| title_full | A single vaccination of nucleoside-modified Rabies mRNA vaccine induces prolonged highly protective immune responses in mice |
| title_fullStr | A single vaccination of nucleoside-modified Rabies mRNA vaccine induces prolonged highly protective immune responses in mice |
| title_full_unstemmed | A single vaccination of nucleoside-modified Rabies mRNA vaccine induces prolonged highly protective immune responses in mice |
| title_short | A single vaccination of nucleoside-modified Rabies mRNA vaccine induces prolonged highly protective immune responses in mice |
| title_sort | single vaccination of nucleoside modified rabies mrna vaccine induces prolonged highly protective immune responses in mice |
| topic | rabies mRNA vaccine rabies virus glycoprotein virus-neutralizing antibodies challenge model |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1099991/full |
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