PO and ID BCG vaccination in humans induce distinct mucosal and systemic immune responses and CD4 T cell transcriptomal molecular signatures.

Publication Type
Journal Article
Year of Publication
Hoft, D F; Xia, M; Zhang, G L; Blazevic, A; Tennant, J; Kaplan, C; Matuschak, G; Dube, T J; Hill, H; Schlesinger, L S; Andersen, P L; Brusic, V
Mucosal Immunol
Date Published
2018 03
Administration, Oral; Adolescent; Adult; Antibodies, Bacterial; BCG Vaccine; CD4 Antigens; Denmark; Female; Follow-Up Studies; Gene Expression Profiling; Humans; Immunity, Mucosal; Immunoglobulin A, Secretory; Injections, Intradermal; Interferon-gamma; Lung; Lymphocyte Activation; Male; Middle Aged; Th1 Cells; Transcriptome; Tuberculosis; Vaccination; Young Adult

Protective efficacy of Bacillus Calmette-Guérin (BCG) may be affected by the methods and routes of vaccine administration. We have studied the safety and immunogenicity of oral (PO) and/or intradermal (ID) administration of BCG in healthy human subjects. No major safety concerns were detected in the 68 healthy adults vaccinated with PO and/or ID BCG. Although both PO and ID BCG could induce systemic Th1 responses capable of IFN-γ production, ID BCG more strongly induced systemic Th1 responses. In contrast, stronger mucosal responses (TB-specific secretory IgA and bronchoalveolar lavage T cells) were induced by PO BCG vaccination. To generate preliminary data comparing the early gene signatures induced by mucosal and systemic BCG vaccination, CD4 memory T cells were isolated from subsets of BCG vaccinated subjects pre- (Day 0) and post-vaccination (Days 7 and 56), rested or stimulated with BCG infected dendritic cells, and then studied by Illumina BeadArray transcriptomal analysis. Notably, distinct gene expression profiles were identified both on Day 7 and Day 56 comparing the PO and ID BCG vaccinated groups by GSEA analysis. Future correlation analyses between specific gene expression patterns and distinct mucosal and systemic immune responses induced will be highly informative for TB vaccine development.