title: B-Cell-Deficient and CD8 T-Cell-Depleted Gnotobiotic Pigs for the Study of Human Rotavirus Vaccine-Induced Protective Immune Responses.
abstract: Genetically modified pigs have become available recently. In this study, we established the gnotobiotic pig model of human rotavirus (HRV) infection using cloned pigs with homozygous disruption in the gene encoding immunoglobulin heavy chain (HCKO), which totally impairs B-cell development. To clarify importance of B cells and cytotoxic T cells in rotavirus immunity, CD8 cells in a subset of the pigs were depleted by injecting antipig CD8 antibodies and the immune phenotypes of all pigs were examined. HCKO pigs, CD8 cell-depleted HCKO pigs, and wild-type (WT) pigs were vaccinated with an attenuated HRV vaccine and challenged with virulent HRV. Protection against HRV infection and diarrhea was assessed postchallenge and detailed T-cell subset responses were determined pre- and postchallenge. Significantly longer duration of virus shedding was seen in vaccinated HCKO pigs than in WT pigs, indicating the importance of B cells in vaccine-induced protective immunity. Vaccinated HCKO/CD8(-) pigs shed significantly higher number of infectious virus than WT pigs and non-CD8-depleted HCKO pigs, indicating the importance of CD8 T cells in controlling virus replication. Therefore, both B cells and CD8 T cells play an important role in the protection against rotavirus infection. HCKO and HCKO/CD8(-) pigs did not differ significantly in diarrhea and virus shedding postchallenge; increased CD4 and CD8(-) γδ T-cell responses probably compensated partially for the lack of CD8 T cells. This study demonstrated that HCKO pigs can serve as a valuable model for dissection of protective immune responses against viral infections and diseases.
authors.affiliation: 1 Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University , Blacksburg, Virginia.
authors.forename: Ke
authors.initials: K
authors.lastname: Wen
authors.affiliation: 1 Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University , Blacksburg, Virginia.
authors.forename: Tammy
authors.initials: T
authors.lastname: Bui
authors.affiliation: 1 Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University , Blacksburg, Virginia.
authors.forename: Mariah
authors.initials: M
authors.lastname: Weiss
authors.affiliation: 1 Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University , Blacksburg, Virginia.
authors.forename: Guohua
authors.initials: G
authors.lastname: Li
authors.affiliation: 1 Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University , Blacksburg, Virginia.
authors.forename: Jacob
authors.initials: J
authors.lastname: Kocher
authors.affiliation: 1 Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University , Blacksburg, Virginia.
authors.forename: Xingdong
authors.initials: X
authors.lastname: Yang
authors.affiliation: 2 Teaching & Research Animal Care Support Service, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University , Blacksburg, Virginia.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Jobst
authors.affiliation: 3 Revivicor, Inc. , Blacksburg, Virginia.
authors.forename: Todd
authors.initials: T
authors.lastname: Vaught
authors.affiliation: 3 Revivicor, Inc. , Blacksburg, Virginia.
authors.forename: Jagdeece
authors.initials: J
authors.lastname: Ramsoondar
authors.affiliation: 3 Revivicor, Inc. , Blacksburg, Virginia.
authors.forename: Suyapa
authors.initials: S
authors.lastname: Ball
authors.affiliation: 4 Department of Large Animal Clinical Sciences, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University , Blacksburg, Virginia.
authors.forename: Sherrie
authors.initials: S
authors.lastname: Clark-Deener
authors.affiliation: 3 Revivicor, Inc. , Blacksburg, Virginia.
authors.forename: David
authors.initials: D
authors.lastname: Ayares
authors.affiliation: 1 Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University , Blacksburg, Virginia.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Yuan
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001402:B-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004195:Disease Models, Animal; D055786:Gene Knockout Techniques; D005856:Germ-Free Life; D047589:Leukocyte Reduction Procedures; D012400:Rotavirus Infections / Q000276:immunology / Q000517:prevention & control*; D022243:Rotavirus Vaccines / Q000008:administration & dosage / Q000276:immunology*; D016511:Severe Combined Immunodeficiency; D013552:Swine
chemical_list: D022243:Rotavirus Vaccines
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