Bronchus-Associated Lymphoid Tissue (BALT) and Survival in a Vaccine Mouse Model of Tularemia 英文参考文献.docVIP

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Bronchus-Associated Lymphoid Tissue (BALT) and Survival in a Vaccine Mouse Model of Tularemia 英文参考文献.doc

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Bronchus-Associated Lymphoid Tissue (BALT) and Survival in a Vaccine Mouse Model of Tularemia 英文参考文献

Bronchus-AssociatedLymphoidTissue(BALT)and SurvivalinaVaccineMouseModelofTularemia DamianaChiavolini1,JavierRangel-Moreno2,GretchenBerg1,KateChristian1,LauraOliveira- Nascimento1,3,SusanWeir1,JosephAlroy4,TroyD.Randall2,LeeM.Wetzler1* 1DepartmentofMedicine,BostonUniversitySchoolofMedicine,Boston,Massachusetts,UnitedStatesofAmerica,2DivisionofAllergy,ImmunologyandRheumatology, UniversityofRochesterMedicalSchool,Rochester,NewYork,UnitedStatesofAmerica,3SchoolofPharmaceuticalSciences,UniversityofSa?o Paulo,Sa?o Paulo,Brazil, 4DepartmentofPathology,TuftsUniversitySchoolofMedicine,CummingsSchoolofVeterinaryMedicineandTuftsMedicalCenter,Boston,Massachusetts,UnitedStates ofAmerica Abstract Background:Francisellatularensiscausesseverepulmonarydisease,andnasalvaccinationcouldbetheidealmeasureto effectively prevent it. Nevertheless, the efficacy of this type of vaccine is influenced by the lack of an effective mucosal adjuvant. Methodology/Principal Findings: Mice were immunized via the nasal route with lipopolysaccharide isolated from F. tularensisandneisserialrecombinantPorBasanadjuvantcandidate.Then,micewerechallengedviathesameroutewith theF.tularensisattenuatedlivevaccinestrain(LVS).Mousesurvivalandanalysisofanumberofimmuneparameterswere conducted following intranasal challenge. Vaccination induced a systemic antibody response and 70% of mice were protected from challenge as showed by their improved survival and weight regain. Lungs from mice recovering from infectionpresentedprominentlymphoidaggregatesinperibronchialandperivascularareas,consistentwiththelocationof bronchus-associated lymphoid tissue (BALT). BALT areas contained proliferating B and T cells, germinal centers, T cell infiltrates, dendritic cells (DCs). We also observed local production of antibody generating cells and homeostatic chemokinesinBALTareas. Conclusions:ThesedataindicatethatPorBmightbeanoptimaladjuvantcandidateforimprovingtheprotectiveeffectofF. tularensis antigens. The presence of B