Journal Article

A novel vaccine strategy to induce mycobacterial antigen-specific Th1 responses by utilizing the C-terminal domain of heat shock protein 70

Tomohiro Uto, Kunio Tsujimura, Masato Uchijima, Shintaro Seto, Toshi Nagata, Takafumi Suda, Kingo Chida, Hirotoshi Nakamura and Yukio Koide

in FEMS Immunology & Medical Microbiology

Published on behalf of Federation of Microbiological Societies

Volume 61, issue 2, pages 189-196
Published in print March 2011 | ISSN: 0928-8244
Published online December 2010 | e-ISSN: 1574-695X | DOI: https://dx.doi.org/10.1111/j.1574-695X.2010.00762.x
A novel vaccine strategy to induce mycobacterial antigen-specific Th1 responses by utilizing the C-terminal domain of heat shock protein 70

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  • Medical Microbiology and Virology
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Abstract

Heat shock protein 70 (HSP70) is a member of a highly conserved superfamily of intracellular chaperones called stress proteins that can activate innate and adaptive immune responses. We evaluated the effect of a fusion DNA vaccine that encoded mycobacterial HSP70 and MPT51, a major secreted protein of Mycobacterium tuberculosis. Spleen cells from mice immunized with fusion DNA of full-length HSP70 and MPT51 produced a higher amount of interferon-γ (IFN-γ) in response to the CD4+, but not the CD8+ T-cell epitope peptide on MPT51 than those from mice immunized with MPT51 DNA. Furthermore, because HSP70 comprises the N-terminal ATPase domain and the C-terminal peptide-binding domain, we attempted to identify the domain responsible for its enhancing effect. The fusion DNA vaccine that encoded the C-terminal domain of HSP70 and MPT51 induced a higher MPT51-specific IFN-γ production by CD4+ T cells than the vaccine that encoded MPT51 alone, whereas that with the N-terminal domain did not. Similar results were obtained by immunization with the fusion proteins. These results suggest that the DNA vaccine that encodes a chimeric antigen molecule fused with mycobacterial HSP70, especially with its C-terminal domain, can induce a stronger antigen-specific T-helper cell type 1 response than antigen DNA alone.

Keywords: Mycobacterium tuberculosis; heat shock protein; DNA vaccine; IFN-γ

Journal Article.  4596 words.  Illustrated.

Subjects: Medical Microbiology and Virology ; Biotechnology ; Genetics and Genomics ; Microbiology ; Molecular and Cell Biology

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