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.
Fil: Nyblade, Charlotte. Virginia-Maryland College of Veterinary Medicine; Estados Unidos
Fil: Hensley, Casey. Virginia-Maryland College of Veterinary Medicine; Estados Unidos
Fil: Parreño, Gladys Viviana. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Virología e Innovaciones Tecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Virología e Innovaciones Tecnológicas; Argentina
Fil: Zhou, Peng. Virginia-Maryland College of Veterinary Medicine; Estados Unidos
Fil: Frazier, Maggie. Virginia-Maryland College of Veterinary Medicine; Estados Unidos
Fil: Frazier, Annie. Virginia-Maryland College of Veterinary Medicine; Estados Unidos
Fil: Ramesh, Ashwin. Virginia-Maryland College of Veterinary Medicine; Estados Unidos
Fil: Lei, Shaohua. Virginia-Maryland College of Veterinary Medicine; Estados Unidos
Fil: Degiuseppe, Juan Ignacio. Universidad Nacional de Santiago del Estero. Facultad de Humanidades Ciencias Sociales y de la Salud. Instituto de Estudios e Investigaciones en Enfermería; Argentina
Fil: Tan, Ming. University of Cincinnati; Estados Unidos
Fil: Yuan, Lijuan. Virginia-Maryland College of Veterinary Medicine; Estados Unidos
Materia
DIARRHEA
GNOTOBIOTIC PIG MODEL
HUMAN ROTAVIRUS
P[6] GENOTYPE
VACCINE EVALUATION
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/221497
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/221497
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
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, LijuanDIARRHEAGNOTOBIOTIC PIG MODELHUMAN ROTAVIRUSP[6] GENOTYPEVACCINE EVALUATIONhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Human 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.Fil: Nyblade, Charlotte. Virginia-Maryland College of Veterinary Medicine; Estados UnidosFil: Hensley, Casey. Virginia-Maryland College of Veterinary Medicine; Estados UnidosFil: Parreño, Gladys Viviana. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Virología e Innovaciones Tecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Virología e Innovaciones Tecnológicas; ArgentinaFil: Zhou, Peng. Virginia-Maryland College of Veterinary Medicine; Estados UnidosFil: Frazier, Maggie. Virginia-Maryland College of Veterinary Medicine; Estados UnidosFil: Frazier, Annie. Virginia-Maryland College of Veterinary Medicine; Estados UnidosFil: Ramesh, Ashwin. Virginia-Maryland College of Veterinary Medicine; Estados UnidosFil: Lei, Shaohua. Virginia-Maryland College of Veterinary Medicine; Estados UnidosFil: Degiuseppe, Juan Ignacio. Universidad Nacional de Santiago del Estero. Facultad de Humanidades Ciencias Sociales y de la Salud. Instituto de Estudios e Investigaciones en Enfermería; ArgentinaFil: Tan, Ming. University of Cincinnati; Estados UnidosFil: Yuan, Lijuan. Virginia-Maryland College of Veterinary Medicine; Estados UnidosMDPI2022-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/221497Nyblade, Charlotte; Hensley, Casey; Parreño, Gladys Viviana; Zhou, Peng; Frazier, Maggie; et al.; A New Gnotobiotic Pig Model of P[6] Human Rotavirus Infection and Disease for Preclinical Evaluation of Rotavirus Vaccines; MDPI; Viruses; 14; 12; 12-2022; 1-111999-4915CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.3390/v14122803info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:00:26Zoai:ri.conicet.gov.ar:11336/221497instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 10:00:26.699CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
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
DIARRHEA
GNOTOBIOTIC PIG MODEL
HUMAN ROTAVIRUS
P[6] GENOTYPE
VACCINE EVALUATION
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 DIARRHEA
GNOTOBIOTIC PIG MODEL
HUMAN ROTAVIRUS
P[6] GENOTYPE
VACCINE EVALUATION
topic DIARRHEA
GNOTOBIOTIC PIG MODEL
HUMAN ROTAVIRUS
P[6] GENOTYPE
VACCINE EVALUATION
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
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.
Fil: Nyblade, Charlotte. Virginia-Maryland College of Veterinary Medicine; Estados Unidos
Fil: Hensley, Casey. Virginia-Maryland College of Veterinary Medicine; Estados Unidos
Fil: Parreño, Gladys Viviana. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Virología e Innovaciones Tecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Virología e Innovaciones Tecnológicas; Argentina
Fil: Zhou, Peng. Virginia-Maryland College of Veterinary Medicine; Estados Unidos
Fil: Frazier, Maggie. Virginia-Maryland College of Veterinary Medicine; Estados Unidos
Fil: Frazier, Annie. Virginia-Maryland College of Veterinary Medicine; Estados Unidos
Fil: Ramesh, Ashwin. Virginia-Maryland College of Veterinary Medicine; Estados Unidos
Fil: Lei, Shaohua. Virginia-Maryland College of Veterinary Medicine; Estados Unidos
Fil: Degiuseppe, Juan Ignacio. Universidad Nacional de Santiago del Estero. Facultad de Humanidades Ciencias Sociales y de la Salud. Instituto de Estudios e Investigaciones en Enfermería; Argentina
Fil: Tan, Ming. University of Cincinnati; Estados Unidos
Fil: Yuan, Lijuan. Virginia-Maryland College of Veterinary Medicine; 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
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/11336/221497
Nyblade, Charlotte; Hensley, Casey; Parreño, Gladys Viviana; Zhou, Peng; Frazier, Maggie; et al.; A New Gnotobiotic Pig Model of P[6] Human Rotavirus Infection and Disease for Preclinical Evaluation of Rotavirus Vaccines; MDPI; Viruses; 14; 12; 12-2022; 1-11
1999-4915
CONICET Digital
CONICET
url http://hdl.handle.net/11336/221497
identifier_str_mv Nyblade, Charlotte; Hensley, Casey; Parreño, Gladys Viviana; Zhou, Peng; Frazier, Maggie; et al.; A New Gnotobiotic Pig Model of P[6] Human Rotavirus Infection and Disease for Preclinical Evaluation of Rotavirus Vaccines; MDPI; Viruses; 14; 12; 12-2022; 1-11
1999-4915
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.3390/v14122803
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.13397

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