Multiple Antigen Peptide Containing B and T Cell Epitopes of F1 Antigen of Yersinia pestis Showed Enhanced Th1 Immune Response in Murine Model

Yersinia pestis is a facultative bacterium that can survive and proliferate inside host macrophages and cause bubonic, pneumonic and systemic infection. Apart from humoral response, cell-mediated protection plays a major role in combating the disease. Fraction 1 capsular antigen (F1-Ag) of Y. pestis has long been exploited as a vaccine candidate. In this study, F1-multiple antigenic peptide (F1-MAP or MAP)-specific cell-mediated and cytokine responses were studied in murine model. MAP consisting of three B and one T cell epitopes of F1-antigen with one palmitoyl residue was synthesized using Fmoc chemistry. Mice were immunized with different formulations of MAP in poly DL-lactide-co-glycolide (PLGA) microspheres. F1-MAP with CpG oligodeoxynucleotide (CpG-ODN) as an adjuvant showed enhanced in vitro T cell proliferation and Th1 (IL-2, IFN-γ and TNF-α) and Th17 (IL-17A) cytokine secretion. Similar formulation also showed significantly higher numbers of cytokine (IL-2, IFN-γ)-secreting cells. Moreover, F1-MAP with CpG formulation showed significantly high (P < 0.001) percentage of CD4⁺ IFN-γ⁺ cells as compared to CD8⁺ IFN-γ⁺ cells, and also more (CD4- IFN-γ)⁺ cells secrete perforin and granzyme as compared to (CD8- IFN-γ)⁺ showing Th1 response. Thus, the study highlights the importance of Th1 cytokine and existence of CD4⁺ and CD8⁺ immune response. This study proposes a new perspective for the development of vaccination strategies for Y. pestis that trigger T cell immune response.