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Infection and Immunity, August 2009, p. 3196-3208, Vol. 77, No. 8
0019-9567/09/$08.00+0 doi:10.1128/IAI.00459-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
A Genetically Engineered Live Attenuated Vaccine of Coccidioides posadasii Protects BALB/c Mice against Coccidioidomycosis
,
Jianmin Xue,1,
Xia Chen,1,
Dale Selby,2
Chiung-Yu Hung,1
Jieh-Juen Yu,1 and
Garry T. Cole1*
Department of Biology and South Texas Center for Emerging Infectious Diseases, University of Texas, San Antonio, Texas 78249,1 Department of Pathology, Wilford Hall Medical Center, Lackland Air Force Base, Texas 782362
Received 23 April 2009/ Returned for modification 9 May 2009/ Accepted 23 May 2009
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.
* Corresponding author. Mailing address: Department of Biology, University of Texas at San Antonio, One UTSA Circle, San Antonio, TX 78249-0662. Phone: (210) 458-7017. Fax: (210) 458-7015. E-mail: garry.cole{at}utsa.edu
Published ahead of print on 1 June 2009.
Supplemental material for this article may be found at http://iai.asm.org/.
Present address: Division of Pulmonary Allergy and Critical Care Medicine, University of Pittsburgh, 3459 Fifth Ave., Pittsburgh, PA 15213.
Present address: Department of Surgery, University of Wisconsin, WIMR 5118, 1111 Highland Ave., Madison, WI 53705.
Infection and Immunity, August 2009, p. 3196-3208, Vol. 77, No. 8
0019-9567/09/$08.00+0 doi:10.1128/IAI.00459-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
Copyright © 2009 by the American Society for Microbiology. For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»