title: A genetically engineered live attenuated vaccine of Coccidioides posadasii protects BALB/c mice against coccidioidomycosis.
abstract: Coccidioidomycosis (also known as San Joaquin Valley fever) is an occupational disease. Workers exposed to outdoor dust which contains spores of the soil-inhabiting fungus have a significantly increased risk of respiratory infection. In addition, people with compromised T-cell immunity, the elderly, and certain racial groups, particularly African-Americans and Filipinos, who live in regions of endemicity in the southwestern United States have an elevated incidence of symptomatic infection caused by inhalation of spores of Coccidioides posadasii or Coccidioides immitis. Recurring epidemics and escalation of medical costs have helped to motivate production of a vaccine against valley fever. The major focus has been the development of a defined, T-cell-reactive, recombinant protein vaccine. However, none of the products described to date have provided full protection to coccidioidal disease-susceptible BALB/c mice. Here we describe the first genetically engineered, live, attenuated vaccine that protects both BALB/c and C57BL/6 mice against coccidioidomycosis. Two chitinase genes (CTS2 and CTS3) were disrupted to yield the attenuated strain, which was unable to endosporulate and was no longer infectious. Vaccinated survivors mounted an immune response characterized by production of both T-helper-1- and T-helper-2-type cytokines. Histology revealed well-formed granulomas and markedly diminished inflammation. Significantly fewer organisms were observed in the lungs of survivors than in those of nonvaccinated mice. Additional investigations are required to further define the nature of the live, attenuated vaccine-induced immunity against Coccidioides infection.
authors.affiliation: Department of Biology and South Texas Center for Emerging Infectious Diseases, University of Texas, San Antonio, 78249, USA.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Xue
authors.forename: Xia
authors.initials: X
authors.lastname: Chen
authors.forename: Dale
authors.initials: D
authors.lastname: Selby
authors.forename: Chiung-Yu
authors.initials: CY
authors.lastname: Hung
authors.forename: Jieh-Juen
authors.initials: JJ
authors.lastname: Yu
authors.forename: Garry T
authors.initials: GT
authors.lastname: Cole
mesh_terms: D000818:Animals; D002688:Chitinases / Q000235:genetics; D003045:Coccidioides / Q000235:genetics* / Q000276:immunology*; D003047:Coccidioidomycosis / Q000453:epidemiology / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D015169:Colony Count, Microbial; D016207:Cytokines / Q000378:metabolism; D004271:DNA, Fungal / Q000737:chemistry / Q000235:genetics; D005656:Fungal Proteins / Q000235:genetics; D005657:Fungal Vaccines / Q000235:genetics* / Q000276:immunology*; D055786:Gene Knockout Techniques; D023061:Gene Order; D006801:Humans; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D017422:Sequence Analysis, DNA; D015206:Southwestern United States / Q000453:epidemiology; D016019:Survival Analysis; D014613:Vaccines, Attenuated / Q000235:genetics / Q000276:immunology
chemical_list: D016207:Cytokines; D004271:DNA, Fungal; D005656:Fungal Proteins; D005657:Fungal Vaccines; D014613:Vaccines, Attenuated; D002688:Chitinases