Combined live oral priming and intramuscular boosting regimen with Rotarix® and a nanoparticle-based trivalent rotavirus vaccine evaluated in gnotobiotic pig models of G4P[6] and G...

Autores
Hensley, Casey; Nyblade, Charlotte; Zhou, Peng; Parreño, Gladys Viviana; Ramesh, Ashwin; Frazier, Annie; Frazier, Maggie; Garrison, Sarah; Fantasia-Davis, Ariana; Cai, Ruiqing; Huang, Peng-Wei; Xia, Ming; Tan, Ming; Yuan, Lijuan
Año de publicación
2023
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Human rotavirus (HRV) is the causative agent of severe dehydrating diarrhea in children under the age of five, resulting in up to 215,000 deaths each year. These deaths almost exclusively occur in low- and middle-income countries where vaccine efficacy is the lowest due to chronic malnutrition, gut dysbiosis, and concurrent enteric viral infection. Parenteral vaccines for HRV are particularly attractive as they avoid many of the concerns associated with currently used live oral vaccines. In this study, a two-dose intramuscular (IM) regimen of the trivalent, nanoparticle-based, nonreplicating HRV vaccine (trivalent S60-VP8*), utilizing the shell (S) domain of the capsid of norovirus as an HRV VP8* antigen display platform, was evaluated for immunogenicity and protective efficacy against P[6] and P[8] HRV using gnotobiotic pig models. A prime–boost strategy using one dose of the oral Rotarix® vaccine, followed by one dose of the IM trivalent nanoparticle vaccine was also evaluated. Both regimens were highly immunogenic in inducing serum virus neutralizing, IgG, and IgA antibodies. The two vaccine regimens failed to confer significant protection against diarrhea; however, the prime–boost regimen significantly shortened the duration of virus shedding in pigs challenged orally with the virulent Wa (G1P[8]) HRV and significantly shortened the mean duration of virus shedding, mean peak titer, and area under the curve of virus shedding after challenge with Arg (G4P[6]) HRV. Prime–boost-vaccinated pigs challenged with P[8] HRV had significantly higher P[8]-specific IgG antibody-secreting cells (ASCs) in the spleen post-challenge. Prime–boost-vaccinated pigs challenged with P[6] HRV had significantly higher numbers of P[6]- and P[8]-specific IgG ASCs in the ileum, as well as significantly higher numbers of P[8]-specific IgA ASCs in the spleen post-challenge. These results suggest the promise of and warrant further investigation into the oral priming and parenteral boosting strategy for future HRV vaccines.
Instituto de Virología
Fil: Hensley, Casey. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados Unidos
Fil: Nyblade, Charlotte. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados Unidos
Fil: Zhou, Peng. 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: Parreño, Gladys Viviana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Ramesh, Ashwin. 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: Frazier, Maggie. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados Unidos
Fil: Garrison, Sarah. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados Unidos
Fil: Fantasia-Davis, Ariana. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados Unidos
Fil: Cai, Ruiqing. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados Unidos
Fil: Huang, Peng-Wei. Cincinnati Children’s Hospital Medical Center. Division of Infectious Diseases; Estados Unidos
Fil: Xia, Ming. Cincinnati Children’s Hospital Medical Center. Division of Infectious Diseases; Estados Unidos
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
Vaccines 11 (5) : 927 (Mayo 2023)
Materia
Rotavirus
Nanoparticles
Gnotobiotic Animals
Swine
Vaccines
Nanopartículas
Animales Notobióticos
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:20.500.12123/15201
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spelling Combined live oral priming and intramuscular boosting regimen with Rotarix® and a nanoparticle-based trivalent rotavirus vaccine evaluated in gnotobiotic pig models of G4P[6] and G1P[8] human rotavirus infectionHensley, CaseyNyblade, CharlotteZhou, PengParreño, Gladys VivianaRamesh, AshwinFrazier, AnnieFrazier, MaggieGarrison, SarahFantasia-Davis, ArianaCai, RuiqingHuang, Peng-WeiXia, MingTan, MingYuan, LijuanRotavirusNanoparticlesGnotobiotic AnimalsSwineVaccinesNanopartículasAnimales NotobióticosCerdoVacunaHuman Rotavirus InfectionInfección por Rotavirus HumanoHuman rotavirus (HRV) is the causative agent of severe dehydrating diarrhea in children under the age of five, resulting in up to 215,000 deaths each year. These deaths almost exclusively occur in low- and middle-income countries where vaccine efficacy is the lowest due to chronic malnutrition, gut dysbiosis, and concurrent enteric viral infection. Parenteral vaccines for HRV are particularly attractive as they avoid many of the concerns associated with currently used live oral vaccines. In this study, a two-dose intramuscular (IM) regimen of the trivalent, nanoparticle-based, nonreplicating HRV vaccine (trivalent S60-VP8*), utilizing the shell (S) domain of the capsid of norovirus as an HRV VP8* antigen display platform, was evaluated for immunogenicity and protective efficacy against P[6] and P[8] HRV using gnotobiotic pig models. A prime–boost strategy using one dose of the oral Rotarix® vaccine, followed by one dose of the IM trivalent nanoparticle vaccine was also evaluated. Both regimens were highly immunogenic in inducing serum virus neutralizing, IgG, and IgA antibodies. The two vaccine regimens failed to confer significant protection against diarrhea; however, the prime–boost regimen significantly shortened the duration of virus shedding in pigs challenged orally with the virulent Wa (G1P[8]) HRV and significantly shortened the mean duration of virus shedding, mean peak titer, and area under the curve of virus shedding after challenge with Arg (G4P[6]) HRV. Prime–boost-vaccinated pigs challenged with P[8] HRV had significantly higher P[8]-specific IgG antibody-secreting cells (ASCs) in the spleen post-challenge. Prime–boost-vaccinated pigs challenged with P[6] HRV had significantly higher numbers of P[6]- and P[8]-specific IgG ASCs in the ileum, as well as significantly higher numbers of P[8]-specific IgA ASCs in the spleen post-challenge. These results suggest the promise of and warrant further investigation into the oral priming and parenteral boosting strategy for future HRV vaccines.Instituto de VirologíaFil: Hensley, Casey. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados UnidosFil: Nyblade, Charlotte. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados UnidosFil: Zhou, Peng. 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: Parreño, Gladys Viviana. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ramesh, Ashwin. 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: Frazier, Maggie. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados UnidosFil: Garrison, Sarah. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados UnidosFil: Fantasia-Davis, Ariana. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados UnidosFil: Cai, Ruiqing. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados UnidosFil: Huang, Peng-Wei. Cincinnati Children’s Hospital Medical Center. Division of Infectious Diseases; Estados UnidosFil: Xia, Ming. Cincinnati Children’s Hospital Medical Center. Division of Infectious Diseases; Estados UnidosFil: 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 UnidosMDPI2023-09-13T13:57:21Z2023-09-13T13:57:21Z2023-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttp://hdl.handle.net/20.500.12123/15201https://www.mdpi.com/2076-393X/11/5/9272076-393Xhttps://doi.org/10.3390/vaccines11050927Vaccines 11 (5) : 927 (Mayo 2023)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)2025-09-04T09:49:56Zoai:localhost:20.500.12123/15201instacron: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 09:49:56.582INTA Digital (INTA) - Instituto Nacional de Tecnología Agropecuariafalse
dc.title.none.fl_str_mv Combined live oral priming and intramuscular boosting regimen with Rotarix® and a nanoparticle-based trivalent rotavirus vaccine evaluated in gnotobiotic pig models of G4P[6] and G1P[8] human rotavirus infection
title Combined live oral priming and intramuscular boosting regimen with Rotarix® and a nanoparticle-based trivalent rotavirus vaccine evaluated in gnotobiotic pig models of G4P[6] and G1P[8] human rotavirus infection
spellingShingle Combined live oral priming and intramuscular boosting regimen with Rotarix® and a nanoparticle-based trivalent rotavirus vaccine evaluated in gnotobiotic pig models of G4P[6] and G1P[8] human rotavirus infection
Hensley, Casey
Rotavirus
Nanoparticles
Gnotobiotic Animals
Swine
Vaccines
Nanopartículas
Animales Notobióticos
Cerdo
Vacuna
Human Rotavirus Infection
Infección por Rotavirus Humano
title_short Combined live oral priming and intramuscular boosting regimen with Rotarix® and a nanoparticle-based trivalent rotavirus vaccine evaluated in gnotobiotic pig models of G4P[6] and G1P[8] human rotavirus infection
title_full Combined live oral priming and intramuscular boosting regimen with Rotarix® and a nanoparticle-based trivalent rotavirus vaccine evaluated in gnotobiotic pig models of G4P[6] and G1P[8] human rotavirus infection
title_fullStr Combined live oral priming and intramuscular boosting regimen with Rotarix® and a nanoparticle-based trivalent rotavirus vaccine evaluated in gnotobiotic pig models of G4P[6] and G1P[8] human rotavirus infection
title_full_unstemmed Combined live oral priming and intramuscular boosting regimen with Rotarix® and a nanoparticle-based trivalent rotavirus vaccine evaluated in gnotobiotic pig models of G4P[6] and G1P[8] human rotavirus infection
title_sort Combined live oral priming and intramuscular boosting regimen with Rotarix® and a nanoparticle-based trivalent rotavirus vaccine evaluated in gnotobiotic pig models of G4P[6] and G1P[8] human rotavirus infection
dc.creator.none.fl_str_mv Hensley, Casey
Nyblade, Charlotte
Zhou, Peng
Parreño, Gladys Viviana
Ramesh, Ashwin
Frazier, Annie
Frazier, Maggie
Garrison, Sarah
Fantasia-Davis, Ariana
Cai, Ruiqing
Huang, Peng-Wei
Xia, Ming
Tan, Ming
Yuan, Lijuan
author Hensley, Casey
author_facet Hensley, Casey
Nyblade, Charlotte
Zhou, Peng
Parreño, Gladys Viviana
Ramesh, Ashwin
Frazier, Annie
Frazier, Maggie
Garrison, Sarah
Fantasia-Davis, Ariana
Cai, Ruiqing
Huang, Peng-Wei
Xia, Ming
Tan, Ming
Yuan, Lijuan
author_role author
author2 Nyblade, Charlotte
Zhou, Peng
Parreño, Gladys Viviana
Ramesh, Ashwin
Frazier, Annie
Frazier, Maggie
Garrison, Sarah
Fantasia-Davis, Ariana
Cai, Ruiqing
Huang, Peng-Wei
Xia, Ming
Tan, Ming
Yuan, Lijuan
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Rotavirus
Nanoparticles
Gnotobiotic Animals
Swine
Vaccines
Nanopartículas
Animales Notobióticos
Cerdo
Vacuna
Human Rotavirus Infection
Infección por Rotavirus Humano
topic Rotavirus
Nanoparticles
Gnotobiotic Animals
Swine
Vaccines
Nanopartículas
Animales Notobióticos
Cerdo
Vacuna
Human Rotavirus Infection
Infección por Rotavirus Humano
dc.description.none.fl_txt_mv Human rotavirus (HRV) is the causative agent of severe dehydrating diarrhea in children under the age of five, resulting in up to 215,000 deaths each year. These deaths almost exclusively occur in low- and middle-income countries where vaccine efficacy is the lowest due to chronic malnutrition, gut dysbiosis, and concurrent enteric viral infection. Parenteral vaccines for HRV are particularly attractive as they avoid many of the concerns associated with currently used live oral vaccines. In this study, a two-dose intramuscular (IM) regimen of the trivalent, nanoparticle-based, nonreplicating HRV vaccine (trivalent S60-VP8*), utilizing the shell (S) domain of the capsid of norovirus as an HRV VP8* antigen display platform, was evaluated for immunogenicity and protective efficacy against P[6] and P[8] HRV using gnotobiotic pig models. A prime–boost strategy using one dose of the oral Rotarix® vaccine, followed by one dose of the IM trivalent nanoparticle vaccine was also evaluated. Both regimens were highly immunogenic in inducing serum virus neutralizing, IgG, and IgA antibodies. The two vaccine regimens failed to confer significant protection against diarrhea; however, the prime–boost regimen significantly shortened the duration of virus shedding in pigs challenged orally with the virulent Wa (G1P[8]) HRV and significantly shortened the mean duration of virus shedding, mean peak titer, and area under the curve of virus shedding after challenge with Arg (G4P[6]) HRV. Prime–boost-vaccinated pigs challenged with P[8] HRV had significantly higher P[8]-specific IgG antibody-secreting cells (ASCs) in the spleen post-challenge. Prime–boost-vaccinated pigs challenged with P[6] HRV had significantly higher numbers of P[6]- and P[8]-specific IgG ASCs in the ileum, as well as significantly higher numbers of P[8]-specific IgA ASCs in the spleen post-challenge. These results suggest the promise of and warrant further investigation into the oral priming and parenteral boosting strategy for future HRV vaccines.
Instituto de Virología
Fil: Hensley, Casey. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados Unidos
Fil: Nyblade, Charlotte. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados Unidos
Fil: Zhou, Peng. 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: Parreño, Gladys Viviana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Ramesh, Ashwin. 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: Frazier, Maggie. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados Unidos
Fil: Garrison, Sarah. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados Unidos
Fil: Fantasia-Davis, Ariana. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados Unidos
Fil: Cai, Ruiqing. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados Unidos
Fil: Huang, Peng-Wei. Cincinnati Children’s Hospital Medical Center. Division of Infectious Diseases; Estados Unidos
Fil: Xia, Ming. Cincinnati Children’s Hospital Medical Center. Division of Infectious Diseases; Estados Unidos
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 the causative agent of severe dehydrating diarrhea in children under the age of five, resulting in up to 215,000 deaths each year. These deaths almost exclusively occur in low- and middle-income countries where vaccine efficacy is the lowest due to chronic malnutrition, gut dysbiosis, and concurrent enteric viral infection. Parenteral vaccines for HRV are particularly attractive as they avoid many of the concerns associated with currently used live oral vaccines. In this study, a two-dose intramuscular (IM) regimen of the trivalent, nanoparticle-based, nonreplicating HRV vaccine (trivalent S60-VP8*), utilizing the shell (S) domain of the capsid of norovirus as an HRV VP8* antigen display platform, was evaluated for immunogenicity and protective efficacy against P[6] and P[8] HRV using gnotobiotic pig models. A prime–boost strategy using one dose of the oral Rotarix® vaccine, followed by one dose of the IM trivalent nanoparticle vaccine was also evaluated. Both regimens were highly immunogenic in inducing serum virus neutralizing, IgG, and IgA antibodies. The two vaccine regimens failed to confer significant protection against diarrhea; however, the prime–boost regimen significantly shortened the duration of virus shedding in pigs challenged orally with the virulent Wa (G1P[8]) HRV and significantly shortened the mean duration of virus shedding, mean peak titer, and area under the curve of virus shedding after challenge with Arg (G4P[6]) HRV. Prime–boost-vaccinated pigs challenged with P[8] HRV had significantly higher P[8]-specific IgG antibody-secreting cells (ASCs) in the spleen post-challenge. Prime–boost-vaccinated pigs challenged with P[6] HRV had significantly higher numbers of P[6]- and P[8]-specific IgG ASCs in the ileum, as well as significantly higher numbers of P[8]-specific IgA ASCs in the spleen post-challenge. These results suggest the promise of and warrant further investigation into the oral priming and parenteral boosting strategy for future HRV vaccines.
publishDate 2023
dc.date.none.fl_str_mv 2023-09-13T13:57:21Z
2023-09-13T13:57:21Z
2023-05
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/20.500.12123/15201
https://www.mdpi.com/2076-393X/11/5/927
2076-393X
https://doi.org/10.3390/vaccines11050927
url http://hdl.handle.net/20.500.12123/15201
https://www.mdpi.com/2076-393X/11/5/927
https://doi.org/10.3390/vaccines11050927
identifier_str_mv 2076-393X
dc.language.none.fl_str_mv eng
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dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
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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 Vaccines 11 (5) : 927 (Mayo 2023)
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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