NDLI: Attenuated Yersinia pseudotuberculosis Carrier Vaccine for Simultaneous Antigen-Specific CD4 and CD8 T-Cell Induction

Content Provider	PubMed Central
Author	Rüssmann, Holger Gerdemann, Ulrike Igwe, Emeka I. Klaus, Panthel Heesemann, Jürgen Sara, Garbom Hans, Wolf-watz Geginat, Gernot
Copyright Year	2003
Abstract	Yersinia pseudotuberculosis employs a type III secretion system for targeting of several virulence factors directly to the cytosol of eukaryotic cells. This protein translocation mechanism mediates the ability of Yersinia to resist phagocytosis and is required for sustained extracellular bacterial replication. In the present study, the Yersinia outer protein E (YopE) was used as a carrier molecule for type III-dependent secretion and translocation of listeriolysin O (LLO) from Listeria monocytogenes. In comparison to wild-type Yersinia, an attenuated Y. pseudotuberculosis yopK-null mutant strain hypertranslocates chimeric YopE/LLO into the cytosol of macrophages, resulting in enhanced major histocompatibility complex (MHC) class I-restricted antigen presentation of an LLO-derived CD8 T-cell epitope. Remarkably, T-cell activation assays also revealed a superior ability of translocated over secreted LLO to induce MHC class II-restricted antigen presentation. These in vitro observations were confirmed after immunization of mice with a single dose of the yopK-null mutant strain. Animals orally inoculated with recombinant Yersinia expressing translocated chimeric YopE/LLO revealed high numbers of gamma interferon-producing LLO-specific CD4 and CD8 T cells. For the first time, it is shown that cytosolic antigen display mediated by an extracellular bacterial carrier vaccine results in simultaneous CD4 and CD8 T-cell priming, conferring protection against an intracellular pathogen.
Related Links	http://dx.doi.org/10.1128/iai.71.6.3463-3472.2003
Ending Page	3472
Page Count	10
Starting Page	3463
File Format	PDF
ISSN	00199567
e-ISSN	10985522
Journal	Infection and Immunity
Issue Number	6
Volume Number	71
Language	English
Publisher	American Society for Microbiology
Publisher Date	2003-06-01
Access Restriction	Open
Rights Holder	American Society for Microbiology
Subject Keyword	Immunology Microbiology Parasitology Infectious Diseases Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Infectious Diseases Parasitology Immunology Microbiology

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