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...

Full description

Saved in:
Bibliographic Details
Main Authors: 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
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:Emerging Microbes and Infections
Subjects:
Online Access:https://www.tandfonline.com/doi/10.1080/22221751.2025.2515406
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850219677890904064
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
work_keys_str_mv AT jinpingniu developmentofanoralguttargetedrabiesviruslikeparticlesrvlpsvaccinewithmucosalimmuneadjuvantltbviadeliveringoflocalizedreleasemicroparticles
AT zhangtingzhao developmentofanoralguttargetedrabiesviruslikeparticlesrvlpsvaccinewithmucosalimmuneadjuvantltbviadeliveringoflocalizedreleasemicroparticles
AT tongzhang developmentofanoralguttargetedrabiesviruslikeparticlesrvlpsvaccinewithmucosalimmuneadjuvantltbviadeliveringoflocalizedreleasemicroparticles
AT qingweiliu developmentofanoralguttargetedrabiesviruslikeparticlesrvlpsvaccinewithmucosalimmuneadjuvantltbviadeliveringoflocalizedreleasemicroparticles
AT liyaohuang developmentofanoralguttargetedrabiesviruslikeparticlesrvlpsvaccinewithmucosalimmuneadjuvantltbviadeliveringoflocalizedreleasemicroparticles
AT shipoli developmentofanoralguttargetedrabiesviruslikeparticlesrvlpsvaccinewithmucosalimmuneadjuvantltbviadeliveringoflocalizedreleasemicroparticles
AT haipengliu developmentofanoralguttargetedrabiesviruslikeparticlesrvlpsvaccinewithmucosalimmuneadjuvantltbviadeliveringoflocalizedreleasemicroparticles
AT shaowenyu developmentofanoralguttargetedrabiesviruslikeparticlesrvlpsvaccinewithmucosalimmuneadjuvantltbviadeliveringoflocalizedreleasemicroparticles
AT linfengli developmentofanoralguttargetedrabiesviruslikeparticlesrvlpsvaccinewithmucosalimmuneadjuvantltbviadeliveringoflocalizedreleasemicroparticles
AT haojia developmentofanoralguttargetedrabiesviruslikeparticlesrvlpsvaccinewithmucosalimmuneadjuvantltbviadeliveringoflocalizedreleasemicroparticles
AT wenyunzheng developmentofanoralguttargetedrabiesviruslikeparticlesrvlpsvaccinewithmucosalimmuneadjuvantltbviadeliveringoflocalizedreleasemicroparticles
AT fengyang developmentofanoralguttargetedrabiesviruslikeparticlesrvlpsvaccinewithmucosalimmuneadjuvantltbviadeliveringoflocalizedreleasemicroparticles
AT xingyuanma developmentofanoralguttargetedrabiesviruslikeparticlesrvlpsvaccinewithmucosalimmuneadjuvantltbviadeliveringoflocalizedreleasemicroparticles