rdf:type |
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lifeskim:mentions |
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pubmed:issue |
8
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pubmed:dateCreated |
2005-7-25
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pubmed:abstractText |
Listeria monocytogenes is a gram-positive intracellular pathogen that can enter phagocytic and nonphagocytic cells and colonize their cytosols. Taking advantage of this property to generate an intracellular vaccine delivery vector, we previously described a mutant strain of L. monocytogenes, Deltadal Deltadat, which is unable to synthesize cell wall by virtue of deletions in two genes (dal and dat) required for d-alanine synthesis. This highly attenuated strain induced long-lived protective systemic and mucosal immune responses in mice when administered in the transient presence of d-alanine. We have now increased the usefulness of this organism as a vaccine vector by use of an inducible complementation system that obviates the need for exogenous d-alanine administration. The strain expresses a copy of the Bacillus subtilis racemase gene under the control of a tightly regulated isopropyl-beta-d-thiogalactopyranoside (IPTG)-inducible promoter present on a multicopy plasmid. This bacterium demonstrates strict dose-dependent growth in the presence of IPTG. After removal of inducer, bacterial growth ceased within two replication cycles. Following infection of mice in the absence of IPTG or d-alanine, the bacterium survived in vivo for less than 3 days. Nevertheless, a single immunization elicited a state of long-lasting protective immunity against wild-type L. monocytogenes and induced a subset of effector listeriolysin O-specific CD11a(+) CD8(+) T cells in spleen and other tissues that was strongly enhanced after secondary immunization. This improved L. monocytogenes vector system may have potential use as a live vaccine against human immunodeficiency virus, other infectious diseases, and cancer.
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pubmed:grant |
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0019-9567
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
73
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
5065-73
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:16041022-Alanine Racemase,
pubmed-meshheading:16041022-Animals,
pubmed-meshheading:16041022-Bacterial Vaccines,
pubmed-meshheading:16041022-CD8-Positive T-Lymphocytes,
pubmed-meshheading:16041022-Fibroblasts,
pubmed-meshheading:16041022-Immunity, Cellular,
pubmed-meshheading:16041022-Listeria monocytogenes,
pubmed-meshheading:16041022-Listeriosis,
pubmed-meshheading:16041022-Mice,
pubmed-meshheading:16041022-Mutation
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pubmed:year |
2005
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pubmed:articleTitle |
Conditional lethality yields a new vaccine strain of Listeria monocytogenes for the induction of cell-mediated immunity.
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pubmed:affiliation |
203C Johnson Pavilion, 3610 Hamilton Walk, Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, N.I.H., Extramural
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