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Beata Clapp, Guan Yang, Bianca L Artiaga, Carol Hoffman, Xinghong Yang, John P Driver, David W Pascual, Swine as a Surrogate Model for Human Brucellosis Following Oropharyngeal Vaccination with a Live Attenuated Brucella melitensis Mutant, The Journal of Immunology, Volume 198, Issue Supplement_1, May 2017, Page 199.7, https://doi.org/10.4049/jimmunol.198.Supp.199.7
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Abstract
Human brucellosis is a global health problem, and no human vaccines exist. Although Brucella infections primarily occur via the oropharynx and the upper respiratory tract mucosa, mucosal aspects of Brucella’s pathogenesis are often ignored. Mucosal vaccination with our live attenuated mutant was found to confer exceptional protection against Brucella challenge. While mice have been instrumental to study immunity to Brucella, they may be less suitable to evaluate mucosal infections. Domestic pigs’ close resemblance to human immune system and anatomical features of the oropharyngeal (OPG) mucosa enables studying mucosal brucellosis in a natural host. To assess our mutant’s immunogenicity, 8 wk-old pigs were vaccinated by directly applying 109 CFUs onto the tonsils and sublingual mucosa plus a buccal injection with 108 CFUs on days 0, 2, and 4, and study was terminated on day 60. Isolated peripheral blood mononuclear cells (PBMCs) on days 0, 15, 23, 35, and 60 as well as terminal head and neck lymphoid tissue lymphocytes were evaluated for IFN-g responses by flow cytometry. The greatest IFN-g came from CD8+ and CD4+ CD8+ T cells, as well as NK cells. Changes in peripheral blood T cells over the course of the response showed a significant reduction in the percentage of total CD4+ T cells, and a significant increase in the percentage of total CD8+ and CD4+ CD8+ T cells. Among the lymphoid tissues examined, with the exception of the tonsils where the IFN-g was mostly derived from CD8+ T cells, IFN-g came from CD4+CD8+ T cells, particularly in the mandibular lymph nodes. Thus, our Brucella mutant is immunogenic in swine and capable of eliciting elevated IFN-g responses following OPG vaccination. Work supported by R03 AI128123 & USDA-NIFA2013-01165.
