Abstract：
:New strategies are needed to develop better tools to control TB, including identification of novel antigens for vaccination. Such Mtb antigens must be expressed during Mtb infection in the major target organ, the lung, and must be capable of eliciting human immune responses. Using genome-wide transcriptomics of Mtb infected lungs we developed data sets and methods to identify IVE-TB (in-vivo expressed Mtb) antigens expressed in the lung. Quantitative expression analysis of 2,068 Mtb genes from the predicted first operons identified the most upregulated IVE-TB genes during in-vivo pulmonary infection. By further analysing high-level conservation among whole-genome sequenced Mtb-complex strains (n = 219) and algorithms predicting HLA-class-Ia and II presented epitopes, we selected the most promising IVE-TB candidate antigens. Several of these were recognized by T-cells from in-vitro Mtb-PPD and ESAT6/CFP10-positive donors by proliferation and multi-cytokine production. This was validated in an independent cohort of latently Mtb-infected individuals. Significant T-cell responses were observed in the absence of IFN-γ-production. Collectively, the results underscore the power of our novel antigen discovery approach in identifying Mtb antigens, including those that induce unconventional T-cell responses, which may provide important novel tools for TB vaccination and biomarker profiling. Our generic approach is applicable to other infectious diseases.
journal_name
Sci Repjournal_title
Scientific reportsauthors
Coppola M,van Meijgaarden KE,Franken KL,Commandeur S,Dolganov G,Kramnik I,Schoolnik GK,Comas I,Lund O,Prins C,van den Eeden SJ,Korsvold GE,Oftung F,Geluk A,Ottenhoff THdoi
10.1038/srep37793subject
Has Abstractpub_date
2016-11-28 00:00:00pages
37793issn
2045-2322pii
srep37793journal_volume
6pub_type
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