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pubmed-article:11292702pubmed:abstractTextCoccidioides immitis antigens which stimulate a T helper cell 1 (Th1) pathway of host immune response are considered to be essential components of a vaccine against coccidioidomycosis. Recombinant urease (rURE) and recombinant heat shock protein 60 (rHSP60) of C. immitis were expressed in Escherichia coli and tested as vaccine candidates in BALB/c mice. A synthetic oligodeoxynucleotide which contained unmethylated CpG dinucleotides and was previously shown to enhance a murine Th1 response was used as an immunoadjuvant. T cells isolated from the spleens and lymph nodes of the rURE- and rHSP60-immune mice showed in vitro proliferative responses to the respective recombinant protein, but only those T lymphocytes from rURE-immunized mice revealed markedly elevated levels of expression of selected Th1-type cytokine genes. BALB/c mice immunized subcutaneously with rURE and subsequently challenged by the intraperitoneal (i.p.) route with a lethal inoculum of C. immitis arthroconidia demonstrated a significant reduction in the level of C. immitis infection compared to control animals. rHSP60 was much less effective as a protective antigen. Evaluation of cytokine gene expression in lung tissue and levels of recombinant urease-specific immunoglobulins (immunoglobulin G1 [IgG1] versus IgG2a) in murine sera at 12 days after challenge provided additional evidence that immunization with rURE stimulated a Th1 response to the pathogen. Urease was further evaluated by expression of the URE gene in a mammalian plasmid vector (pSecTag2A.URE) which was used to immunize mice by the intradermal route. In this case, 82% of the vector construct-immunized animals survived more than 40 days after i.p. infection, compared to only 10% of the mice immunized with the vector alone. In addition, 87% of the pSecTag2A.URE-immunized survivors had sterile lungs and spleens. These data support the need for further evaluation of the C. immitis urease as a candidate vaccine against coccidioidomycosis.lld:pubmed
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pubmed-article:11292702pubmed:authorpubmed-author:LiKKlld:pubmed
pubmed-article:11292702pubmed:authorpubmed-author:HuntC FCFlld:pubmed
pubmed-article:11292702pubmed:authorpubmed-author:LehmannP FPFlld:pubmed
pubmed-article:11292702pubmed:authorpubmed-author:ColeG TGTlld:pubmed
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pubmed-article:11292702pubmed:articleTitleRecombinant urease and urease DNA of Coccidioides immitis elicit an immunoprotective response against coccidioidomycosis in mice.lld:pubmed
pubmed-article:11292702pubmed:affiliationDepartment of Microbiology and Immunology, Medical College of Ohio, Toledo, Ohio 43614-5806, USA.lld:pubmed
pubmed-article:11292702pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:11292702pubmed:publicationTypeResearch Support, U.S. Gov't, P.H.S.lld:pubmed
pubmed-article:11292702pubmed:publicationTypeResearch Support, Non-U.S. Gov'tlld:pubmed
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