Recombinant Urease and Urease DNA of Coccidioides immitis Elicit an Immunoprotective Response against Coccidioidomycosis in Mice

Date
2001-05-01
Authors
Li, Kun
Yu, Jieh-Juen
Hung, Chiung-Yu
Lehmann, Paul F.
Cole, Garry T.
Journal Title
Journal ISSN
Volume Title
Publisher
American Society for Microbiology
Abstract

Coccidioides 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 theURE 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.

Description
Keywords
coccidioidomycosis, Coccidioides immitis, Coccidioides, murine model
Citation
Li, K., Yu, J.-J., Hung, C.-Y., Lehmann, P. F., & Cole, G. T. (2001). Recombinant Urease and Urease DNA of Coccidioides immitis Elicit an Immunoprotective Response against Coccidioidomycosis in Mice. Infection and Immunity, 69(5), 2878-2887. doi:10.1128/iai.69.5.2878-2887.2001
Department
Molecular Microbiology and Immunology