BpOmpW Antigen Stimulates the Necessary Immune Correlates of Protection Against Melioidosis

作者: McClean S , Dunachie Sj , Altmann D , Butler D , Reynolds C

DOI: 10.1101/2021.05.16.444297

关键词: Natural killer T cellImmunologyAntigenFOXP3T cellAdjuvantIL-2 receptorCytotoxic T cellELISPOTMedicine

摘要: SUMMMARYMelioidosis is a fatal disease caused by Burkholderia pseudomallei Gram-negative bacteria. It the causative of 89,000 deaths per year in endemic areas Southeast Asia and Northern Australia. Diabetes mellitus most risk factor, increasing 12-fold susceptibility for severe disease. IFN-{gamma} responses from CD4 CD8 T cells, but also NK NKT cells are necessary to eliminate pathogen. Elucidating immune correlates protection our previously described protective BpOmpW vaccine an essential step any before clinical trials. Thus, we immunized non-insulin resistant C57BL/6j mice insulin mouse model Type 2 (T2D) with using Sigma Adjuvant System (SAS) (treatment) or SAS only (control). Two weeks later bloods spleens were collected serological analysis & vitro exposure splenocytes antigen 60 hours performed both controls treatment groups finally analyze stained flow cytometry. induced strong antibody response, stimulated effector CD4+ CD8+ CD25+ Foxp3+regulatory produced higher CD4+, CD8+, relative control group mice. cell comparable those In addition, as precursor its evaluation human studies, humanised HLA-DR HLA-DQ transgenic elicited recall ELISPoT-based study PBMCs donors that contact seven days experienced proliferation. Finally, plasma melioidosis survivors diabetes recognized antigen. Overall, these range approaches used strongly indicate elicits required combat bring closer

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