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

Horváti, Kata and Pályi, Bernadett and Henczkó, Judit and Balka, Gyula and Szabó, Eleonóra and Farkas, Viktor and Biri-Kovács, Beáta and Szeder, Bálint and Fodor, Kinga (2019) A Convenient Synthetic Method to Improve Immunogenicity of Mycobacterium tuberculosis Related T-Cell Epitope Peptides. Vaccines, 7. p. 101. ISSN 2076-393X

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Abstract

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 e�cacy 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- , IL-2, and IL-10 cytokines was measured for the palmitoylated conjugate. Furthermore, the pal-A(P)I conjugate showed relevant vaccine e�cacy against Mycobacterium tuberculosis infection.

Item Type: Article
Subjects: Q Science / természettudomány > QD Chemistry / kémia
Q Science / természettudomány > QR Microbiology / mikrobiológia > QR180 Immunology / immunológia
Depositing User: Viktor Farkas
Date Deposited: 25 Sep 2019 13:41
Last Modified: 03 Apr 2023 06:35
URI: http://real.mtak.hu/id/eprint/101247

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