Development of an oral gut-targeted rabies virus-like particles (RVLPs) vaccine with mucosal immune adjuvant LTB via delivering of localized-release microparticles
Rabies, a fatal zoonotic infectious diseases caused by rabies virus (RABV) infection, still has a high incidence with no effective cure in many Asian countries, even though numerous commercial vaccines have been administered for decades. One of the most important reasons is the neglected that main r...
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Taylor & Francis Group
2025-12-01
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| Series: | Emerging Microbes and Infections |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/22221751.2025.2515406 |
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| author | Jinping Niu Zhangting Zhao Tong Zhang Qingwei Liu Liyao Huang Shipo Li Haipeng Liu Shaowen Yu Linfeng Li Hao Jia Wenyun Zheng Feng Yang Xingyuan Ma |
| author_facet | Jinping Niu Zhangting Zhao Tong Zhang Qingwei Liu Liyao Huang Shipo Li Haipeng Liu Shaowen Yu Linfeng Li Hao Jia Wenyun Zheng Feng Yang Xingyuan Ma |
| author_sort | Jinping Niu |
| collection | DOAJ |
| description | Rabies, a fatal zoonotic infectious diseases caused by rabies virus (RABV) infection, still has a high incidence with no effective cure in many Asian countries, even though numerous commercial vaccines have been administered for decades. One of the most important reasons is the neglected that main reservoirs of RABV, such as many stray and wild animals, are inaccessible for effective vaccination, especially in natural wilderness environments. In this study, we developed a highly effective gut-targeted oral rabies vaccine (ORV), which containing the immunoadjuvant LTB by targeted administration of microparticles with local release in the intestine. Based on the virus like particles (RVLPs) were assembled by RABV glycoprotein (RVGP) and matrix protein (RVMP), the enterically released microparticles ELPGA MPs loaded with RVLPs and djuvant LTB (RVLPs + LTB/EPLGA MPs) were prepared and demonstrated the ability of intestinal targeting which released in a pH-dependent manner. Subsequently, in vivo immunoassay experiments showed that the levels of anti-RVLPs IgG, IFN-γ and IL-4 were significantly higher in the RVLPs + LTB/EPLGA MPs groups than in the normal saline group or positive control group (R group) after intragastric administration. Moreover, higher levels of CD4+/CD8+ T cells ratios in the peripheral blood and sIgA in the intestines and feces of mice indicated that RVLPs + LTB/EPLGA MPs group elicited a stronger cellular immune response and mucosal immunity. In short, the novel oral vaccine is exploring valuable strategies of oral gut-targeted vaccines and promising to effectively prevent the spread of RABV among terrestrial carnivorous animals and human populations. |
| format | Article |
| id | doaj-art-76b39f6551744ec78ecb3a04b4bf6fd7 |
| institution | OA Journals |
| issn | 2222-1751 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Emerging Microbes and Infections |
| spelling | doaj-art-76b39f6551744ec78ecb3a04b4bf6fd72025-08-20T02:07:19ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512025-12-0114110.1080/22221751.2025.2515406Development of an oral gut-targeted rabies virus-like particles (RVLPs) vaccine with mucosal immune adjuvant LTB via delivering of localized-release microparticlesJinping Niu0Zhangting Zhao1Tong Zhang2Qingwei Liu3Liyao Huang4Shipo Li5Haipeng Liu6Shaowen Yu7Linfeng Li8Hao Jia9Wenyun Zheng10Feng Yang11Xingyuan Ma12State Key Laboratory of Bioreactor engineering, East China University of Science and Technology, Shanghai, People’s Republic of ChinaState Key Laboratory of Bioreactor engineering, East China University of Science and Technology, Shanghai, People’s Republic of ChinaShanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, People’s Republic of ChinaShanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, People’s Republic of ChinaShanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, People’s Republic of ChinaState Key Laboratory of Bioreactor engineering, East China University of Science and Technology, Shanghai, People’s Republic of ChinaState Key Laboratory of Marine Environmental Science, Xiamen University, Xiamen, People’s Republic of ChinaSchool of Mathematics, East China University of Science and Technology, Shanghai, People’s Republic of ChinaState Key Laboratory of Bioreactor engineering, East China University of Science and Technology, Shanghai, People’s Republic of ChinaSchool of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of ChinaShanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, People’s Republic of ChinaSchool of Pharmacy, Naval Medical University, Shanghai, People’s Republic of ChinaState Key Laboratory of Bioreactor engineering, East China University of Science and Technology, Shanghai, People’s Republic of ChinaRabies, a fatal zoonotic infectious diseases caused by rabies virus (RABV) infection, still has a high incidence with no effective cure in many Asian countries, even though numerous commercial vaccines have been administered for decades. One of the most important reasons is the neglected that main reservoirs of RABV, such as many stray and wild animals, are inaccessible for effective vaccination, especially in natural wilderness environments. In this study, we developed a highly effective gut-targeted oral rabies vaccine (ORV), which containing the immunoadjuvant LTB by targeted administration of microparticles with local release in the intestine. Based on the virus like particles (RVLPs) were assembled by RABV glycoprotein (RVGP) and matrix protein (RVMP), the enterically released microparticles ELPGA MPs loaded with RVLPs and djuvant LTB (RVLPs + LTB/EPLGA MPs) were prepared and demonstrated the ability of intestinal targeting which released in a pH-dependent manner. Subsequently, in vivo immunoassay experiments showed that the levels of anti-RVLPs IgG, IFN-γ and IL-4 were significantly higher in the RVLPs + LTB/EPLGA MPs groups than in the normal saline group or positive control group (R group) after intragastric administration. Moreover, higher levels of CD4+/CD8+ T cells ratios in the peripheral blood and sIgA in the intestines and feces of mice indicated that RVLPs + LTB/EPLGA MPs group elicited a stronger cellular immune response and mucosal immunity. In short, the novel oral vaccine is exploring valuable strategies of oral gut-targeted vaccines and promising to effectively prevent the spread of RABV among terrestrial carnivorous animals and human populations.https://www.tandfonline.com/doi/10.1080/22221751.2025.2515406Oral gut-targetedrabies virus-like particles (RVLPs)mucosal immune vaccineslocalized-release microparticlesLTB B subunit of heat-labile toxin (LTB)PLGA/Eudradit microparticle (EPLGA MPs) |
| spellingShingle | Jinping Niu Zhangting Zhao Tong Zhang Qingwei Liu Liyao Huang Shipo Li Haipeng Liu Shaowen Yu Linfeng Li Hao Jia Wenyun Zheng Feng Yang Xingyuan Ma Development of an oral gut-targeted rabies virus-like particles (RVLPs) vaccine with mucosal immune adjuvant LTB via delivering of localized-release microparticles Emerging Microbes and Infections Oral gut-targeted rabies virus-like particles (RVLPs) mucosal immune vaccines localized-release microparticles LTB B subunit of heat-labile toxin (LTB) PLGA/Eudradit microparticle (EPLGA MPs) |
| title | Development of an oral gut-targeted rabies virus-like particles (RVLPs) vaccine with mucosal immune adjuvant LTB via delivering of localized-release microparticles |
| title_full | Development of an oral gut-targeted rabies virus-like particles (RVLPs) vaccine with mucosal immune adjuvant LTB via delivering of localized-release microparticles |
| title_fullStr | Development of an oral gut-targeted rabies virus-like particles (RVLPs) vaccine with mucosal immune adjuvant LTB via delivering of localized-release microparticles |
| title_full_unstemmed | Development of an oral gut-targeted rabies virus-like particles (RVLPs) vaccine with mucosal immune adjuvant LTB via delivering of localized-release microparticles |
| title_short | Development of an oral gut-targeted rabies virus-like particles (RVLPs) vaccine with mucosal immune adjuvant LTB via delivering of localized-release microparticles |
| title_sort | development of an oral gut targeted rabies virus like particles rvlps vaccine with mucosal immune adjuvant ltb via delivering of localized release microparticles |
| topic | Oral gut-targeted rabies virus-like particles (RVLPs) mucosal immune vaccines localized-release microparticles LTB B subunit of heat-labile toxin (LTB) PLGA/Eudradit microparticle (EPLGA MPs) |
| url | https://www.tandfonline.com/doi/10.1080/22221751.2025.2515406 |
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