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Design and Characterization of a Multistage Peptide-Based Vaccine Platform to Target Mycobacterium tuberculosis Infection
[Image: see text] The complex immunopathology ofMycobacterium 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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10587871/ https://www.ncbi.nlm.nih.gov/pubmed/37606258 http://dx.doi.org/10.1021/acs.bioconjchem.3c00273 |
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author | Bellini, Chiara Vergara, Emil Bencs, Fruzsina Fodor, Kinga Bősze, Szilvia Krivić, Denis Bacsa, Bernadett Surguta, Sára Eszter Tóvári, József Reljic, Rajko Horváti, Kata |
author_facet | Bellini, Chiara Vergara, Emil Bencs, Fruzsina Fodor, Kinga Bősze, Szilvia Krivić, Denis Bacsa, Bernadett Surguta, Sára Eszter Tóvári, József Reljic, Rajko Horváti, Kata |
author_sort | Bellini, Chiara |
collection | PubMed |
description | [Image: see text] The complex immunopathology ofMycobacterium 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. |
format | Online Article Text |
id | pubmed-10587871 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-105878712023-10-21 Design and Characterization of a Multistage Peptide-Based Vaccine Platform to Target Mycobacterium tuberculosis Infection Bellini, Chiara Vergara, Emil Bencs, Fruzsina Fodor, Kinga Bősze, Szilvia Krivić, Denis Bacsa, Bernadett Surguta, Sára Eszter Tóvári, József Reljic, Rajko Horváti, Kata Bioconjug Chem [Image: see text] The complex immunopathology ofMycobacterium 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. American Chemical Society 2023-08-22 /pmc/articles/PMC10587871/ /pubmed/37606258 http://dx.doi.org/10.1021/acs.bioconjchem.3c00273 Text en © 2023 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by/4.0/Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Bellini, Chiara Vergara, Emil Bencs, Fruzsina Fodor, Kinga Bősze, Szilvia Krivić, Denis Bacsa, Bernadett Surguta, Sára Eszter Tóvári, József Reljic, Rajko Horváti, Kata Design and Characterization of a Multistage Peptide-Based Vaccine Platform to Target Mycobacterium tuberculosis Infection |
title | Design and Characterization of a Multistage Peptide-Based
Vaccine Platform to Target Mycobacterium tuberculosis Infection |
title_full | Design and Characterization of a Multistage Peptide-Based
Vaccine Platform to Target Mycobacterium tuberculosis Infection |
title_fullStr | Design and Characterization of a Multistage Peptide-Based
Vaccine Platform to Target Mycobacterium tuberculosis Infection |
title_full_unstemmed | Design and Characterization of a Multistage Peptide-Based
Vaccine Platform to Target Mycobacterium tuberculosis Infection |
title_short | Design and Characterization of a Multistage Peptide-Based
Vaccine Platform to Target Mycobacterium tuberculosis Infection |
title_sort | design and characterization of a multistage peptide-based
vaccine platform to target mycobacterium tuberculosis infection |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10587871/ https://www.ncbi.nlm.nih.gov/pubmed/37606258 http://dx.doi.org/10.1021/acs.bioconjchem.3c00273 |
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