| Autor: |
Bellini C; MTA-TTK Lendület 'Momentum' Peptide-Based Vaccines Research Group, Institute of Materials and Environmental Chemistry, Research Centre for Natural Sciences, Budapest 1117, Hungary.; Hevesy György PhD School of Chemistry, Eötvös Loránd University, Budapest 1117, Hungary., Vergara E; Institute for Infection and Immunity, St. George's, University of London, London SW17 0RE, U.K., Bencs F; Hevesy György PhD School of Chemistry, Eötvös Loránd University, Budapest 1117, Hungary.; Laboratory of Structural Chemistry and Biology, Institute of Chemistry, Eötvös Loránd University, Budapest 1117, Hungary., Fodor K; Department of Laboratory Animal Science and Animal Protection, University of Veterinary Medicine, Budapest 1078, Hungary., Bősze S; ELKH-ELTE Research Group of Peptide Chemistry, Eötvös Loránd Research Network (ELKH), Eötvös Loránd University, Budapest 1117, Hungary., Krivić D; Division of Medical Physics and Biophysics, Gottfried Schatz Research Center, Medical University of Graz, 8010 Graz, Austria., Bacsa B; Division of Medical Physics and Biophysics, Gottfried Schatz Research Center, Medical University of Graz, 8010 Graz, Austria., Surguta SE; Department of Experimental Pharmacology and National Tumor Biology Laboratory, National Institute of Oncology, Budapest 1122, Hungary., Tóvári J; Department of Experimental Pharmacology and National Tumor Biology Laboratory, National Institute of Oncology, Budapest 1122, Hungary., Reljic R; Institute for Infection and Immunity, St. George's, University of London, London SW17 0RE, U.K., Horváti K; MTA-TTK Lendület 'Momentum' Peptide-Based Vaccines Research Group, Institute of Materials and Environmental Chemistry, Research Centre for Natural Sciences, Budapest 1117, Hungary. |
| Abstrakt: |
The complex immunopathology of Mycobacterium tuberculosis ( Mtb ) is one of the main challenges in developing a novel vaccine against this pathogen, particularly regarding eliciting protection against both active and latent stages. Multistage vaccines, which contain antigens expressed in both phases, represent a promising strategy for addressing this issue, as testified by the tuberculosis vaccine clinical pipeline. Given this approach, we designed and characterized a multistage peptide-based vaccine platform containing CD4+ and CD8+ T cell epitopes previously validated for inducing a relevant T cell response against Mtb . After preliminary screening, CFP10 (32-39), GlfT2 (4-12), HBHA (185-194), and PPE15 (1-15) were selected as promising candidates, and we proved that the PM1 pool of these peptides triggered a T cell response in Mtb -sensitized human peripheral blood mononuclear cells (PBMCs). Taking advantage of the use of thiol-maleimide chemoselective ligation, we synthesized a multiepitope conjugate ( Ac-CGHP ). Our results showed a structure-activity relationship between the conjugation and a higher tendency to fold and assume an ordered secondary structure. Moreover, the palmitoylated conjugate ( Pal-CGHP ) comprising the same peptide antigens was associated with an enhanced cellular uptake in human and murine antigen-presenting cells and a better immunogenicity profile. Immunization study, conducted in BALB/c mice, showed that Pal-CGHP induced a significantly higher T cell proliferation and production of IFNγ and TNFα over PM1 formulated in the Sigma Adjuvant System. |
