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After mucosal infection, brucellosis develops into a systemic disease. Mucosal vaccination could offer a viable alternative to conventional injection practices to deter disease. Using a nasal vaccination approach, the <jats:italic>\u0394znuA B. melitensis<\/jats:italic> was found to confer potent protection against pulmonary <jats:italic>Brucella<\/jats:italic> challenge, and reduce colonization of spleens and lungs by more than 2500\u2010fold, with &gt;50% of vaccinated mice showing no detectable brucellae. Furthermore, 10\u2010fold more brucellae\u2010specific, interferon\u2010\u03b3 (IFN\u2010\u03b3)\u2010producing CD8<jats:sup>+<\/jats:sup> T cells than CD4<jats:sup>+<\/jats:sup> T cells were induced in the spleen and respiratory lymph nodes. Evaluation of pulmonary and splenic CD8<jats:sup>+<\/jats:sup> T cells from mice vaccinated with <jats:italic>\u0394znuA B. melitensis<\/jats:italic> revealed that these expressed an activated effector memory (CD44<jats:sup>hi<\/jats:sup>CD62L<jats:sup>lo<\/jats:sup>CCR7<jats:sup>lo<\/jats:sup>) T cells producing elevated levels of IFN\u2010\u03b3, tumor necrosis factor\u2010\u03b1, perforin and granzyme B. To assess the relative importance of these increased numbers of CD8<jats:sup>+<\/jats:sup> T cells, CD8<jats:sup>\u2212\/\u2212<\/jats:sup> mice were challenged with virulent <jats:italic>B. melitensis<\/jats:italic>, and they showed markedly increased bacterial loads in organs in contrast to similarly challenged CD4<jats:sup>\u2212\/\u2212<\/jats:sup> mice. Only <jats:italic>\u0394znuA B. melitensis<\/jats:italic> <jats:italic>\u2010<\/jats:italic> and Rev\u20101\u2010vaccinated CD4<jats:sup>\u2212\/\u2212<\/jats:sup> and wild\u2010type mice, not CD8<jats:sup>\u2212\/\u2212<\/jats:sup> mice, were completely protected against <jats:italic>Brucella<\/jats:italic> challenge. Determination of cytokines responsible for conferring protection showed the relative importance of IFN\u2010\u03b3, but not interleukin\u201017 (IL\u201017). Unlike wild\u2010type (wt) mice, IL\u201017 was greatly induced in IFN\u2010\u03b3<jats:sup>\u2212\/\u2212<\/jats:sup> mice, but IL\u201017 could not substitute for IFN\u2010\u03b3's protection, although an increase in brucellae dissemination was observed upon <jats:italic>in vivo<\/jats:italic> IL\u201017 neutralization. These results show that nasal <jats:italic>\u0394znuA B. melitensis<\/jats:italic> vaccination represents an attractive means to stimulate systemic and mucosal immune protection via CD8<jats:sup>+<\/jats:sup> T\u2010cell engagement.<\/jats:p>","DOI":"10.1038\/icb.2016.5","type":"journal-article","created":{"date-parts":[[2016,1,11]],"date-time":"2016-01-11T09:20:04Z","timestamp":1452504004000},"page":"496-508","source":"Crossref","is-referenced-by-count":31,"title":["Nasal vaccination stimulates CD8<sup>+<\/sup> T cells for potent protection against mucosal <i>Brucella melitensis<\/i> challenge"],"prefix":"10.1111","volume":"94","author":[{"given":"Beata","family":"Clapp","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases and Pathology, University of Florida  Gainesville FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinghong","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and 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