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Open AccessArticle

A Convenient Synthetic Method to Improve Immunogenicity of Mycobacterium tuberculosis Related T-Cell Epitope Peptides

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MTA-ELTE Research Group of Peptide Chemistry, Eötvös Loránd University, Hungarian Academy of Sciences, Budapest 1117, Hungary
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Institute of Chemistry, Eötvös Loránd University, Budapest 1117, Hungary
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National Biosafety Laboratory, National Public Health Center, Budapest 1097, Hungary
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Department of Pathology, University of Veterinary Medicine, Budapest 1078, Hungary
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Laboratory of Bacteriology, Korányi National Institute for Tuberculosis and Respiratory Medicine, Budapest 1122, Hungary
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MTA-ELTE Protein Modelling Research Group, Eötvös Loránd University, Hungarian Academy of Sciences, Budapest 1117, Hungary
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Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest 1117, Hungary
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Department of Laboratory Animal and Animal Protection, University of Veterinary Medicine, Budapest 1078, Hungary
*
Author to whom correspondence should be addressed.
Vaccines 2019, 7(3), 101; https://doi.org/10.3390/vaccines7030101
Received: 27 June 2019 / Revised: 15 August 2019 / Accepted: 20 August 2019 / Published: 27 August 2019
(This article belongs to the Section Vaccines against Infectious Diseases)
Epitopes from different proteins expressed by Mycobacterium tuberculosis (Rv1886c, Rv0341, Rv3873) were selected based on previously reported antigenic properties. Relatively short linear T-cell epitope peptides generally have unordered structure, limited immunogenicity, and low in vivo stability. Therefore, they rely on proper formulation and on the addition of adjuvants. Here we report a convenient synthetic route to induce a more potent immune response by the formation of a trivalent conjugate in spatial arrangement. Chemical and structural characterization of the vaccine conjugates was followed by the study of cellular uptake and localization. Immune response was assayed by the measurement of splenocyte proliferation and cytokine production, while vaccine efficacy was studied in a murine model of tuberculosis. The conjugate showed higher tendency to fold and increased internalization rate into professional antigen presenting cells compared to free epitopes. Cellular uptake was further improved by the incorporation of a palmitoyl group to the conjugate and the resulted pal-A(P)I derivative possessed an internalization rate 10 times higher than the free epitope peptides. Vaccination of CB6F1 mice with free peptides resulted in low T-cell response. In contrast, significantly higher T-cell proliferation with prominent expression of IFN-γ, IL-2, and IL-10 cytokines was measured for the palmitoylated conjugate. Furthermore, the pal-A(P)I conjugate showed relevant vaccine efficacy against Mycobacterium tuberculosis infection. View Full-Text
Keywords: T-cell epitope; maleimide conjugation; Mycobacterium tuberculosis; peptide-based vaccines; tuftsin T-cell epitope; maleimide conjugation; Mycobacterium tuberculosis; peptide-based vaccines; tuftsin
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Horváti, K.; Pályi, B.; Henczkó, J.; Balka, G.; Szabó, E.; Farkas, V.; Biri-Kovács, B.; Szeder, B.; Fodor, K. A Convenient Synthetic Method to Improve Immunogenicity of Mycobacterium tuberculosis Related T-Cell Epitope Peptides. Vaccines 2019, 7, 101.

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