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...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-12-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/14/12/2803 |
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| author | Charlotte Nyblade Casey Hensley Viviana Parreño Peng Zhou Maggie Frazier Annie Frazier Ashwin Ramesh Shaohua Lei Juan Ignacio Degiuseppe Ming Tan Lijuan Yuan |
| author_facet | Charlotte Nyblade Casey Hensley Viviana Parreño Peng Zhou Maggie Frazier Annie Frazier Ashwin Ramesh Shaohua Lei Juan Ignacio Degiuseppe Ming Tan Lijuan Yuan |
| author_sort | Charlotte Nyblade |
| collection | DOAJ |
| 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 × 10<sup>5</sup> 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<sup>−2</sup>, 10<sup>3</sup>, 10<sup>4</sup>, and 10<sup>5</sup> 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 10<sup>5</sup> 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. |
| first_indexed | 2024-03-09T15:44:48Z |
| format | Article |
| id | doaj.art-745d7653ce9a4b738c8551a573175d7d |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-09T15:44:48Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-745d7653ce9a4b738c8551a573175d7d2023-11-24T18:39:57ZengMDPI AGViruses1999-49152022-12-011412280310.3390/v14122803A New Gnotobiotic Pig Model of P[6] Human Rotavirus Infection and Disease for Preclinical Evaluation of Rotavirus VaccinesCharlotte Nyblade0Casey Hensley1Viviana Parreño2Peng Zhou3Maggie Frazier4Annie Frazier5Ashwin Ramesh6Shaohua Lei7Juan Ignacio Degiuseppe8Ming Tan9Lijuan Yuan10Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA 24060, USADepartment of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA 24060, USADepartment of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA 24060, USADepartment of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA 24060, USADepartment of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA 24060, USADepartment of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA 24060, USADepartment of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA 24060, USADepartment of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA 24060, USALaboratory of Viral Gastroenteritis, National Institute for Infectious Diseases (INEI-ANLIS “Dr. Carlos G. Malbrán”), Ciudad Autónoma de Buenos Aires 1281, ArgentinaDivision of Infectious Diseases, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USADepartment of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA 24060, USAHuman 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 × 10<sup>5</sup> 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<sup>−2</sup>, 10<sup>3</sup>, 10<sup>4</sup>, and 10<sup>5</sup> 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 10<sup>5</sup> 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.https://www.mdpi.com/1999-4915/14/12/2803human rotavirusP[6] genotypegnotobiotic pig modeldiarrheavaccine evaluation |
| spellingShingle | Charlotte Nyblade Casey Hensley Viviana Parreño Peng Zhou Maggie Frazier Annie Frazier Ashwin Ramesh Shaohua Lei Juan Ignacio Degiuseppe Ming Tan Lijuan Yuan A New Gnotobiotic Pig Model of P[6] Human Rotavirus Infection and Disease for Preclinical Evaluation of Rotavirus Vaccines Viruses human rotavirus P[6] genotype gnotobiotic pig model diarrhea vaccine evaluation |
| 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 | human rotavirus P[6] genotype gnotobiotic pig model diarrhea vaccine evaluation |
| url | https://www.mdpi.com/1999-4915/14/12/2803 |
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