Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Bellini, C; Vergara, E; Bencs, F; Fodor, K; Bosze, S; Krivic, D; Bacsa, B; Surguta, SE; Tovari, J; Reljic, R; Horvaati, K.
Design and Characterization of a Multistage Peptide-Based Vaccine Platform to Target Mycobacterium tuberculosis Infection
BIOCONJUGATE CHEM. 2023;
Doi: 10.1021/acs.bioconjchem.3c00273
[OPEN ACCESS]
Web of Science
PubMed
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- Co-Autor*innen der Med Uni Graz
- Bacsa Bernadett
- Krivic Denis
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- Abstract:
- The complex immunopathologyofMycobacterium tuberculosis(Mtb) is one of the main challenges in developinga novel vaccine against this pathogen, particularly regarding elicitingprotection against both active and latent stages. Multistage vaccines,which contain antigens expressed in both phases, represent a promisingstrategy for addressing this issue, as testified by the tuberculosisvaccine clinical pipeline. Given this approach, we designed and characterizeda multistage peptide-based vaccine platform containing CD4+ and CD8+T cell epitopes previously validated for inducing a relevant T cellresponse against Mtb. After preliminary screening,CFP10 (32-39), GlfT2 (4-12), HBHA (185-194),and PPE15 (1-15) were selected as promising candidates, andwe proved that the PM1 pool of these peptides triggereda T cell response in Mtb-sensitized human peripheralblood mononuclear cells (PBMCs). Taking advantage of the use of thiol-maleimidechemoselective ligation, we synthesized a multiepitope conjugate (Ac-CGHP). Our results showed a structure-activity relationshipbetween the conjugation and a higher tendency to fold and assume anordered secondary structure. Moreover, the palmitoylated conjugate(Pal-CGHP) comprising the same peptide antigens was associatedwith an enhanced cellular uptake in human and murine antigen-presentingcells and a better immunogenicity profile. Immunization study, conductedin BALB/c mice, showed that Pal-CGHP induced a significantlyhigher T cell proliferation and production of IFN & gamma; and TNF & alpha;over PM1 formulated in the Sigma Adjuvant System.