title: Multiple antigen peptide containing B and T cell epitopes of F1 antigen of Yersinia pestis showed enhanced Th1 immune response in murine model.
abstract: 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.
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences AIIMS, New Delhi-110029, India.
authors.forename: R
authors.initials: R
authors.lastname: Ali
authors.forename: R A
authors.initials: RA
authors.lastname: Naqvi
authors.forename: S
authors.initials: S
authors.lastname: Kumar
authors.forename: A A
authors.initials: AA
authors.lastname: Bhat
authors.forename: D N
authors.initials: DN
authors.lastname: Rao
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation; D018985:Epitopes, B-Lymphocyte / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism; D007376:Interleukin-2 / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000276:immunology; D010455:Peptides / Q000737:chemistry / Q000276:immunology*; D010930:Plague / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control; D010931:Plague Vaccine / Q000008:administration & dosage / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism; D015010:Yersinia pestis / Q000276:immunology
chemical_list: D001426:Bacterial Proteins; C408982:CPG-oligonucleotide; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D020381:Interleukin-17; D007376:Interleukin-2; D009838:Oligodeoxyribonucleotides; D010455:Peptides; D010931:Plague Vaccine; D014409:Tumor Necrosis Factor-alpha; C086725:caf1 protein, Yersinia pestis; D007371:Interferon-gamma