A new gnotobiotic pig model of P[6] human rotavirus infection and disease for preclinical evaluation of rotavirus vaccines
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 develop...
| Autores principales: | , , , , , , , , , , |
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| Formato: | info:ar-repo/semantics/artículo |
| Lenguaje: | Inglés |
| Publicado: |
MDPI
2023
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| Materias: | |
| Acceso en línea: | http://hdl.handle.net/20.500.12123/16366 https://www.mdpi.com/1999-4915/14/12/2803 https://doi.org/10.3390/v14122803 |
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| author | 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_browse | Degiuseppe, Juan Ignacio Frazier, Annie Frazier, Maggie Hensley, Casey Lei, Shaohua Nyblade, Charlotte Parreño, Gladys Viviana Ramesh, Ashwin Tan, Ming Yuan, Lijuan Zhou, Peng |
| 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_sort | Nyblade, Charlotte |
| collection | INTA Digital |
| 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. |
| format | info:ar-repo/semantics/artículo |
| id | INTA16366 |
| institution | Instituto Nacional de Tecnología Agropecuaria (INTA -Argentina) |
| language | Inglés |
| publishDate | 2023 |
| publishDateRange | 2023 |
| publishDateSort | 2023 |
| publisher | MDPI |
| publisherStr | MDPI |
| record_format | dspace |
| spelling | INTA163662023-12-27T14:26:36Z A new gnotobiotic pig model of P[6] human rotavirus infection and disease for preclinical evaluation of rotavirus vaccines Nyblade, Charlotte Hensley, Casey Parreño, Gladys Viviana Zhou, Peng Frazier, Maggie Frazier, Annie Ramesh, Ashwin Lei, Shaohua Degiuseppe, Juan Ignacio Tan, Ming Yuan, Lijuan Rotavirus Gnotobiotic Animals Diarrhoea Swine Vaccines Animales Notobióticos Diarrea Cerdo Vacuna Human Rotavirus Infection Infección por Rotavirus Humano 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 2023-12-27T14:22:43Z 2023-12-27T14:22:43Z 2022-12 info:ar-repo/semantics/artículo info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion 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 eng 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) application/pdf MDPI Viruses 14 (12) : 2803 (2022) |
| spellingShingle | Rotavirus Gnotobiotic Animals Diarrhoea Swine Vaccines Animales Notobióticos Diarrea Cerdo Vacuna Human Rotavirus Infection Infección por Rotavirus Humano Nyblade, Charlotte Hensley, Casey Parreño, Gladys Viviana Zhou, Peng Frazier, Maggie Frazier, Annie Ramesh, Ashwin Lei, Shaohua Degiuseppe, Juan Ignacio Tan, Ming Yuan, Lijuan 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 |
| 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_short | A new gnotobiotic pig model of P[6] human rotavirus infection and disease for preclinical evaluation of rotavirus vaccines |
| title_sort | new gnotobiotic pig model of p 6 human rotavirus infection and disease for preclinical evaluation of rotavirus vaccines |
| topic | Rotavirus Gnotobiotic Animals Diarrhoea Swine Vaccines Animales Notobióticos Diarrea Cerdo Vacuna Human Rotavirus Infection Infección por Rotavirus Humano |
| url | http://hdl.handle.net/20.500.12123/16366 https://www.mdpi.com/1999-4915/14/12/2803 https://doi.org/10.3390/v14122803 |
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