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Infect. Immun. doi:10.1128/IAI.00753-07
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

VACCINATION WITH HEAT SHOCK PROTEIN 60 INDUCES A PROTECTIVE IMMUNE RESPONSE AGAINST EXPERIMENTAL Paracoccidioides brasiliensis PULMONARY INFECTION

Laboratório de Biologia Molecular, ICBII, Universidade Federal de Goiás, 74001-970 Goiânia, Goiás, Brazil; Veterans Affairs Hospital, Division of Infectious Diseases, Department of Medicine, University of Cincinnati, College of Medicine, Cincinnati, Ohio 45267-0560

^* To whom correspondence should be addressed. Email: george.deepe{at}uc.edu.

	Abstract

Paracoccidioides brasiliensis causes a chronic granulomatous mycosis prevalent in Latin America. Successful resolution of infection with this fungus is dependent on activation of cellular immunity. We previously identified heat shock protein 60 as a target of the humoral response in paracoccidioidomycosis. Herein we expressed the gene encoding the heat shock protein 60 in Escherichia coli and analyzed the immunological activity of this recombinant antigen. Immunization of BALB/c mice with recombinant protein emulsified in adjuvant stimulated a cellular immune response. Splenocytes from immunized mice proliferated in response to antigen and released interleukin-12 and interferon-gamma. Vaccination with heat shock protein 60 reduced fungal burden in mice given 10⁶ or 10⁷ yeasts and protected mice from a lethal challenge. The efficacy of vaccination was blunted by neutralization of interferon-gamma. CD4⁺ cells were necessary for the efficacy of vaccination in both the afferent and efferent phases. Thus, we have demonstrated that this immunodominant antigen is a candidate for development of a vaccine against this fungus.