A new gnotobiotic pig model of P[6] human rotavirus infection and disease for preclinical evaluation of rotavirus vaccines

Autores
Nyblade, Charlotte; Hensley, Casey; Parreño, Gladys Viviana; Zhou, Peng; Frazier, Maggie; Frazier, Annie; Ramesh, Ashwin; Lei, Shaohua; Degiuseppe, Juan Ignacio; Tan, Ming; Yuan, Lijuan
Año de publicación
2022
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Human rotavirus (HRV) is a leading cause of gastroenteritis in children under 5 years of age. Licensed vaccines containing G1P[8] and G1-4P[8] strains are less efficacious against newly emerging P[6] strains, indicating an urgent need for better cross protective vaccines. Here, we report our development of a new gnotobiotic (Gn) pig model of P[6] HRV infection and disease as a tool for evaluating potential vaccine candidates. The Arg HRV (G4P[6]) strain was derived from a diarrheic human infant stool sample and determined to be free of other viruses by metagenomic sequencing. Neonatal Gn pigs were orally inoculated with the stool suspension containing 5.6 × 105 fluorescent focus units (FFU) of the virus. Small and large intestinal contents were collected at post inoculation day 2 or 3. The virus was passaged 6 times in neonatal Gn pigs to generate a large inoculum pool. Next, 33–34 day old Gn pigs were orally inoculated with 10−2, 103, 104, and 105 FFU of Arg HRV to determine the optimal challenge dose. All pigs developed clinical signs of infection, regardless of the inoculum dose. The optimal challenge dose was determined to be 105 FFU. This new Gn pig model is ready to be used to assess the protective efficacy of candidate monovalent and multivalent vaccines against P[6] HRV.
Instituto de Virología
Fil: Nyblade, Charlotte. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados Unidos
Fil: Hensley, Casey. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados Unidos
Fil: Parreño, Gladys Viviana. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados Unidos
Fil: Parreño, Gladys Viviana. Instituto Nacional de Tecnología Agropecuaria (INTA). INCUINTA. Instituto de Virologia e Innovaciones Tecnologicas (IVIT); Argentina
Fil: Zhou, Peng. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados Unidos
Fil: Frazier, Maggie. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados Unidos
Fil: Frazier, Annie. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados Unidos
Fil: Ramesh, Ashwin. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados Unidos
Fil: Lei, Shaohua. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados Unidos
Fil: Degiuseppe, Juan Ignacio. Administración Nacional de Laboratorios e Institutos de Salud (ANLIS). Instituto Nacional de Enfermedades Infecciosas “Dr. Carlos G. Malbrán” (INEI). Laboratorio de Gastroenteritis Virales; Argentina
Fil: Tan, Ming. Cincinnati Children’s Hospital Medical Center. Division of Infectious Diseases; Estados Unidos
Fil: Tan, Ming. University of Cincinnati College of Medicine. Department of Pediatrics; Estados Unidos
Fil: Yuan, Lijuan. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados Unidos
Fuente
Viruses 14 (12) : 2803 (2022)
Materia
Rotavirus
Gnotobiotic Animals
Diarrhoea
Swine
Vaccines
Animales Notobióticos
Diarrea
Cerdo
Vacuna
Human Rotavirus Infection
Infección por Rotavirus Humano
Nivel de accesibilidad
acceso abierto
Condiciones de uso
http://creativecommons.org/licenses/by-nc-sa/4.0/
Repositorio
INTA Digital (INTA)
Institución
Instituto Nacional de Tecnología Agropecuaria
OAI Identificador
oai:localhost:20.500.12123/16366
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oai_identifier_str oai:localhost:20.500.12123/16366
network_acronym_str INTADig
repository_id_str l
network_name_str INTA Digital (INTA)
spelling A new gnotobiotic pig model of P[6] human rotavirus infection and disease for preclinical evaluation of rotavirus vaccinesNyblade, CharlotteHensley, CaseyParreño, Gladys VivianaZhou, PengFrazier, MaggieFrazier, AnnieRamesh, AshwinLei, ShaohuaDegiuseppe, Juan IgnacioTan, MingYuan, LijuanRotavirusGnotobiotic AnimalsDiarrhoeaSwineVaccinesAnimales NotobióticosDiarreaCerdoVacunaHuman Rotavirus InfectionInfección por Rotavirus HumanoHuman rotavirus (HRV) is a leading cause of gastroenteritis in children under 5 years of age. Licensed vaccines containing G1P[8] and G1-4P[8] strains are less efficacious against newly emerging P[6] strains, indicating an urgent need for better cross protective vaccines. Here, we report our development of a new gnotobiotic (Gn) pig model of P[6] HRV infection and disease as a tool for evaluating potential vaccine candidates. The Arg HRV (G4P[6]) strain was derived from a diarrheic human infant stool sample and determined to be free of other viruses by metagenomic sequencing. Neonatal Gn pigs were orally inoculated with the stool suspension containing 5.6 × 105 fluorescent focus units (FFU) of the virus. Small and large intestinal contents were collected at post inoculation day 2 or 3. The virus was passaged 6 times in neonatal Gn pigs to generate a large inoculum pool. Next, 33–34 day old Gn pigs were orally inoculated with 10−2, 103, 104, and 105 FFU of Arg HRV to determine the optimal challenge dose. All pigs developed clinical signs of infection, regardless of the inoculum dose. The optimal challenge dose was determined to be 105 FFU. This new Gn pig model is ready to be used to assess the protective efficacy of candidate monovalent and multivalent vaccines against P[6] HRV.Instituto de VirologíaFil: Nyblade, Charlotte. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados UnidosFil: Hensley, Casey. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados UnidosFil: Parreño, Gladys Viviana. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados UnidosFil: Parreño, Gladys Viviana. Instituto Nacional de Tecnología Agropecuaria (INTA). INCUINTA. Instituto de Virologia e Innovaciones Tecnologicas (IVIT); ArgentinaFil: Zhou, Peng. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados UnidosFil: Frazier, Maggie. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados UnidosFil: Frazier, Annie. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados UnidosFil: Ramesh, Ashwin. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados UnidosFil: Lei, Shaohua. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados UnidosFil: Degiuseppe, Juan Ignacio. Administración Nacional de Laboratorios e Institutos de Salud (ANLIS). Instituto Nacional de Enfermedades Infecciosas “Dr. Carlos G. Malbrán” (INEI). Laboratorio de Gastroenteritis Virales; ArgentinaFil: Tan, Ming. Cincinnati Children’s Hospital Medical Center. Division of Infectious Diseases; Estados UnidosFil: Tan, Ming. University of Cincinnati College of Medicine. Department of Pediatrics; Estados UnidosFil: Yuan, Lijuan. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados UnidosMDPI2023-12-27T14:22:43Z2023-12-27T14:22:43Z2022-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttp://hdl.handle.net/20.500.12123/16366https://www.mdpi.com/1999-4915/14/12/28031999-4915https://doi.org/10.3390/v14122803Viruses 14 (12) : 2803 (2022)reponame:INTA Digital (INTA)instname:Instituto Nacional de Tecnología Agropecuariaenginfo:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-nc-sa/4.0/Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)2025-09-04T09:50:08Zoai:localhost:20.500.12123/16366instacron:INTAInstitucionalhttp://repositorio.inta.gob.ar/Organismo científico-tecnológicoNo correspondehttp://repositorio.inta.gob.ar/oai/requesttripaldi.nicolas@inta.gob.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:l2025-09-04 09:50:09.533INTA Digital (INTA) - Instituto Nacional de Tecnología Agropecuariafalse
dc.title.none.fl_str_mv A new gnotobiotic pig model of P[6] human rotavirus infection and disease for preclinical evaluation of rotavirus vaccines
title A new gnotobiotic pig model of P[6] human rotavirus infection and disease for preclinical evaluation of rotavirus vaccines
spellingShingle A new gnotobiotic pig model of P[6] human rotavirus infection and disease for preclinical evaluation of rotavirus vaccines
Nyblade, Charlotte
Rotavirus
Gnotobiotic Animals
Diarrhoea
Swine
Vaccines
Animales Notobióticos
Diarrea
Cerdo
Vacuna
Human Rotavirus Infection
Infección por Rotavirus Humano
title_short A new gnotobiotic pig model of P[6] human rotavirus infection and disease for preclinical evaluation of rotavirus vaccines
title_full A new gnotobiotic pig model of P[6] human rotavirus infection and disease for preclinical evaluation of rotavirus vaccines
title_fullStr A new gnotobiotic pig model of P[6] human rotavirus infection and disease for preclinical evaluation of rotavirus vaccines
title_full_unstemmed A new gnotobiotic pig model of P[6] human rotavirus infection and disease for preclinical evaluation of rotavirus vaccines
title_sort A new gnotobiotic pig model of P[6] human rotavirus infection and disease for preclinical evaluation of rotavirus vaccines
dc.creator.none.fl_str_mv Nyblade, Charlotte
Hensley, Casey
Parreño, Gladys Viviana
Zhou, Peng
Frazier, Maggie
Frazier, Annie
Ramesh, Ashwin
Lei, Shaohua
Degiuseppe, Juan Ignacio
Tan, Ming
Yuan, Lijuan
author Nyblade, Charlotte
author_facet Nyblade, Charlotte
Hensley, Casey
Parreño, Gladys Viviana
Zhou, Peng
Frazier, Maggie
Frazier, Annie
Ramesh, Ashwin
Lei, Shaohua
Degiuseppe, Juan Ignacio
Tan, Ming
Yuan, Lijuan
author_role author
author2 Hensley, Casey
Parreño, Gladys Viviana
Zhou, Peng
Frazier, Maggie
Frazier, Annie
Ramesh, Ashwin
Lei, Shaohua
Degiuseppe, Juan Ignacio
Tan, Ming
Yuan, Lijuan
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Rotavirus
Gnotobiotic Animals
Diarrhoea
Swine
Vaccines
Animales Notobióticos
Diarrea
Cerdo
Vacuna
Human Rotavirus Infection
Infección por Rotavirus Humano
topic Rotavirus
Gnotobiotic Animals
Diarrhoea
Swine
Vaccines
Animales Notobióticos
Diarrea
Cerdo
Vacuna
Human Rotavirus Infection
Infección por Rotavirus Humano
dc.description.none.fl_txt_mv Human rotavirus (HRV) is a leading cause of gastroenteritis in children under 5 years of age. Licensed vaccines containing G1P[8] and G1-4P[8] strains are less efficacious against newly emerging P[6] strains, indicating an urgent need for better cross protective vaccines. Here, we report our development of a new gnotobiotic (Gn) pig model of P[6] HRV infection and disease as a tool for evaluating potential vaccine candidates. The Arg HRV (G4P[6]) strain was derived from a diarrheic human infant stool sample and determined to be free of other viruses by metagenomic sequencing. Neonatal Gn pigs were orally inoculated with the stool suspension containing 5.6 × 105 fluorescent focus units (FFU) of the virus. Small and large intestinal contents were collected at post inoculation day 2 or 3. The virus was passaged 6 times in neonatal Gn pigs to generate a large inoculum pool. Next, 33–34 day old Gn pigs were orally inoculated with 10−2, 103, 104, and 105 FFU of Arg HRV to determine the optimal challenge dose. All pigs developed clinical signs of infection, regardless of the inoculum dose. The optimal challenge dose was determined to be 105 FFU. This new Gn pig model is ready to be used to assess the protective efficacy of candidate monovalent and multivalent vaccines against P[6] HRV.
Instituto de Virología
Fil: Nyblade, Charlotte. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados Unidos
Fil: Hensley, Casey. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados Unidos
Fil: Parreño, Gladys Viviana. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados Unidos
Fil: Parreño, Gladys Viviana. Instituto Nacional de Tecnología Agropecuaria (INTA). INCUINTA. Instituto de Virologia e Innovaciones Tecnologicas (IVIT); Argentina
Fil: Zhou, Peng. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados Unidos
Fil: Frazier, Maggie. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados Unidos
Fil: Frazier, Annie. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados Unidos
Fil: Ramesh, Ashwin. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados Unidos
Fil: Lei, Shaohua. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados Unidos
Fil: Degiuseppe, Juan Ignacio. Administración Nacional de Laboratorios e Institutos de Salud (ANLIS). Instituto Nacional de Enfermedades Infecciosas “Dr. Carlos G. Malbrán” (INEI). Laboratorio de Gastroenteritis Virales; Argentina
Fil: Tan, Ming. Cincinnati Children’s Hospital Medical Center. Division of Infectious Diseases; Estados Unidos
Fil: Tan, Ming. University of Cincinnati College of Medicine. Department of Pediatrics; Estados Unidos
Fil: Yuan, Lijuan. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados Unidos
description Human rotavirus (HRV) is a leading cause of gastroenteritis in children under 5 years of age. Licensed vaccines containing G1P[8] and G1-4P[8] strains are less efficacious against newly emerging P[6] strains, indicating an urgent need for better cross protective vaccines. Here, we report our development of a new gnotobiotic (Gn) pig model of P[6] HRV infection and disease as a tool for evaluating potential vaccine candidates. The Arg HRV (G4P[6]) strain was derived from a diarrheic human infant stool sample and determined to be free of other viruses by metagenomic sequencing. Neonatal Gn pigs were orally inoculated with the stool suspension containing 5.6 × 105 fluorescent focus units (FFU) of the virus. Small and large intestinal contents were collected at post inoculation day 2 or 3. The virus was passaged 6 times in neonatal Gn pigs to generate a large inoculum pool. Next, 33–34 day old Gn pigs were orally inoculated with 10−2, 103, 104, and 105 FFU of Arg HRV to determine the optimal challenge dose. All pigs developed clinical signs of infection, regardless of the inoculum dose. The optimal challenge dose was determined to be 105 FFU. This new Gn pig model is ready to be used to assess the protective efficacy of candidate monovalent and multivalent vaccines against P[6] HRV.
publishDate 2022
dc.date.none.fl_str_mv 2022-12
2023-12-27T14:22:43Z
2023-12-27T14:22:43Z
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12123/16366
https://www.mdpi.com/1999-4915/14/12/2803
1999-4915
https://doi.org/10.3390/v14122803
url http://hdl.handle.net/20.500.12123/16366
https://www.mdpi.com/1999-4915/14/12/2803
https://doi.org/10.3390/v14122803
identifier_str_mv 1999-4915
dc.language.none.fl_str_mv eng
language eng
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-sa/4.0/
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-sa/4.0/
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv Viruses 14 (12) : 2803 (2022)
reponame:INTA Digital (INTA)
instname:Instituto Nacional de Tecnología Agropecuaria
reponame_str INTA Digital (INTA)
collection INTA Digital (INTA)
instname_str Instituto Nacional de Tecnología Agropecuaria
repository.name.fl_str_mv INTA Digital (INTA) - Instituto Nacional de Tecnología Agropecuaria
repository.mail.fl_str_mv tripaldi.nicolas@inta.gob.ar
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score 12.623145

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