Preliminary evaluation of a novel serotype O foot-and-mouth disease mRNA vaccine

Foot-and-mouth disease virus (FMDV) is one of the most significant animal pathogens worldwide, severely impacting the health and productivity of pigs, cattle, sheep, and other ungulates. Although the traditional vaccines have played a crucial role in epidemic control, inactivated vaccines face persi...

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Main Authors: Jingang Zhao, Peng Xiao, Aiguo Xin, Heran Zhu, Hao Wang, Jinlong Xiao, Hong Gao
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-04-01
Series:Frontiers in Microbiology
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Online Access:https://www.frontiersin.org/articles/10.3389/fmicb.2025.1503191/full
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author Jingang Zhao
Jingang Zhao
Peng Xiao
Aiguo Xin
Aiguo Xin
Heran Zhu
Heran Zhu
Hao Wang
Jinlong Xiao
Hong Gao
Hong Gao
author_facet Jingang Zhao
Jingang Zhao
Peng Xiao
Aiguo Xin
Aiguo Xin
Heran Zhu
Heran Zhu
Hao Wang
Jinlong Xiao
Hong Gao
Hong Gao
author_sort Jingang Zhao
collection DOAJ
description Foot-and-mouth disease virus (FMDV) is one of the most significant animal pathogens worldwide, severely impacting the health and productivity of pigs, cattle, sheep, and other ungulates. Although the traditional vaccines have played a crucial role in epidemic control, inactivated vaccines face persistent challenges concerning the potential for virus dissemination and pressures from serotype and subtype matching. However, the manufacture of attenuated vaccines is forbidden, and the efficiency of alternative vaccines for immune protection is still inadequate. Consequently, there exists an urgent need for safer and more effective innovative vaccines in animal husbandry. In this study, we aimed to develop a lipid nanoparticle mRNA vaccine based on VP1-3A-3D epitopes from serotype O FMD and to verify its specific expression within cytoplasmic and injection sites. Our findings demonstrated that mRNA transfected into primary spleen cells derived from guinea pigs induced cytokine release, promoted differentiation of both CD4+ T and CD8+ T lymphocytes, and enhanced lymphocyte proliferation rates. Following immunization of mRNA vaccine in guinea pigs, we observed increased differentiation of both CD4+ T and CD8+ T cells, alongside elevated levels of cytokine secretion. Additionally, this vaccination induced the production of specific IgG antibodies as well as neutralizing antibodies. Importantly, our vaccine provided complete protection for all six guinea pigs against a lethal challenge of 100 GPID50, with histopathological scores indicating protection equivalent to that conferred by the inactivated vaccine. The viral load results demonstrated that the vaccine group significantly reduced viral copy numbers in serum and effectively decreased the concentration of the inflammatory cytokine IL-1β. Furthermore, during the pre-immune phase following vaccination with the mRNA vaccine in pigs, heightened cytokine secretion was observed, along with the inhibition of viral replication. Simultaneously, the neutralizing antibody titer in the serum remained stable over 4 months. Immunofluorescence analysis of spleen tissues from both guinea pigs and pigs demonstrated marked activation and increased expression of CD4+ and CD8+ T lymphocytes, as well as macrophages, in the mRNA vaccine group. In summary, this study suggests that the serotype O FMD mRNA vaccine is a promising candidate for further development in the fight against FMDV.
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publisher Frontiers Media S.A.
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series Frontiers in Microbiology
spelling doaj-art-6b80b6f46c8e475d9c9e48704a26c71c2025-08-20T02:19:38ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2025-04-011610.3389/fmicb.2025.15031911503191Preliminary evaluation of a novel serotype O foot-and-mouth disease mRNA vaccineJingang Zhao0Jingang Zhao1Peng Xiao2Aiguo Xin3Aiguo Xin4Heran Zhu5Heran Zhu6Hao Wang7Jinlong Xiao8Hong Gao9Hong Gao10College of Animal Science and Technology, Yunnan Agricultural University, Kunming, ChinaYunnan Tropical and Subtropical Animal Virus Disease Laboratory, Yunnan Academy of Animal Husbandry and Veterinary Sciences, Kunming, ChinaCollege of Veterinary Medicine, Yunnan Agricultural University, Kunming, ChinaYunnan Tropical and Subtropical Animal Virus Disease Laboratory, Yunnan Academy of Animal Husbandry and Veterinary Sciences, Kunming, ChinaNational Foot-and-Mouth Disease Para-Reference Laboratory (Kunming), Yunnan Academy of Animal Husbandry and Veterinary Sciences, Kunming, ChinaYunnan Tropical and Subtropical Animal Virus Disease Laboratory, Yunnan Academy of Animal Husbandry and Veterinary Sciences, Kunming, ChinaNational Foot-and-Mouth Disease Para-Reference Laboratory (Kunming), Yunnan Academy of Animal Husbandry and Veterinary Sciences, Kunming, ChinaCollege of Veterinary Medicine, Yunnan Agricultural University, Kunming, ChinaCollege of Veterinary Medicine, Yunnan Agricultural University, Kunming, ChinaCollege of Animal Science and Technology, Yunnan Agricultural University, Kunming, ChinaCollege of Veterinary Medicine, Yunnan Agricultural University, Kunming, ChinaFoot-and-mouth disease virus (FMDV) is one of the most significant animal pathogens worldwide, severely impacting the health and productivity of pigs, cattle, sheep, and other ungulates. Although the traditional vaccines have played a crucial role in epidemic control, inactivated vaccines face persistent challenges concerning the potential for virus dissemination and pressures from serotype and subtype matching. However, the manufacture of attenuated vaccines is forbidden, and the efficiency of alternative vaccines for immune protection is still inadequate. Consequently, there exists an urgent need for safer and more effective innovative vaccines in animal husbandry. In this study, we aimed to develop a lipid nanoparticle mRNA vaccine based on VP1-3A-3D epitopes from serotype O FMD and to verify its specific expression within cytoplasmic and injection sites. Our findings demonstrated that mRNA transfected into primary spleen cells derived from guinea pigs induced cytokine release, promoted differentiation of both CD4+ T and CD8+ T lymphocytes, and enhanced lymphocyte proliferation rates. Following immunization of mRNA vaccine in guinea pigs, we observed increased differentiation of both CD4+ T and CD8+ T cells, alongside elevated levels of cytokine secretion. Additionally, this vaccination induced the production of specific IgG antibodies as well as neutralizing antibodies. Importantly, our vaccine provided complete protection for all six guinea pigs against a lethal challenge of 100 GPID50, with histopathological scores indicating protection equivalent to that conferred by the inactivated vaccine. The viral load results demonstrated that the vaccine group significantly reduced viral copy numbers in serum and effectively decreased the concentration of the inflammatory cytokine IL-1β. Furthermore, during the pre-immune phase following vaccination with the mRNA vaccine in pigs, heightened cytokine secretion was observed, along with the inhibition of viral replication. Simultaneously, the neutralizing antibody titer in the serum remained stable over 4 months. Immunofluorescence analysis of spleen tissues from both guinea pigs and pigs demonstrated marked activation and increased expression of CD4+ and CD8+ T lymphocytes, as well as macrophages, in the mRNA vaccine group. In summary, this study suggests that the serotype O FMD mRNA vaccine is a promising candidate for further development in the fight against FMDV.https://www.frontiersin.org/articles/10.3389/fmicb.2025.1503191/fullFMDmRNA vaccineimmune protectionguinea pigpig
spellingShingle Jingang Zhao
Jingang Zhao
Peng Xiao
Aiguo Xin
Aiguo Xin
Heran Zhu
Heran Zhu
Hao Wang
Jinlong Xiao
Hong Gao
Hong Gao
Preliminary evaluation of a novel serotype O foot-and-mouth disease mRNA vaccine
Frontiers in Microbiology
FMD
mRNA vaccine
immune protection
guinea pig
pig
title Preliminary evaluation of a novel serotype O foot-and-mouth disease mRNA vaccine
title_full Preliminary evaluation of a novel serotype O foot-and-mouth disease mRNA vaccine
title_fullStr Preliminary evaluation of a novel serotype O foot-and-mouth disease mRNA vaccine
title_full_unstemmed Preliminary evaluation of a novel serotype O foot-and-mouth disease mRNA vaccine
title_short Preliminary evaluation of a novel serotype O foot-and-mouth disease mRNA vaccine
title_sort preliminary evaluation of a novel serotype o foot and mouth disease mrna vaccine
topic FMD
mRNA vaccine
immune protection
guinea pig
pig
url https://www.frontiersin.org/articles/10.3389/fmicb.2025.1503191/full
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