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Infection and Immunity, September 2008, p. 4214-4221, Vol. 76, No. 9
0019-9567/08/$08.00+0     doi:10.1128/IAI.00753-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Vaccination with Heat Shock Protein 60 Induces a Protective Immune Response against Experimental Paracoccidioides brasiliensis Pulmonary Infection{triangledown}

Renata de Bastos Ascenço Soares,1,2 Francisco J. Gomez,2 Célia Maria de Almeida Soares,1 and George S. Deepe Jr.2*

Laboratório de Biologia Molecular, ICBII, Universidade Federal de Goiás, 74001-970 Goiânia, Goiás, Brazil,1 Veterans Affairs Hospital, Division of Infectious Diseases, Department of Medicine, University of Cincinnati, College of Medicine, Cincinnati, Ohio 45267-05602

Received 4 June 2007/ Returned for modification 9 July 2007/ Accepted 2 July 2008

Paracoccidioides brasiliensis causes a chronic granulomatous mycosis prevalent in Latin America. The successful resolution of infection with this fungus is dependent on the activation of cellular immunity. We previously identified heat shock protein 60 (HSP60) as a target of the humoral response in paracoccidioidomycosis. Herein we expressed the gene encoding HSP60 in Escherichia coli and analyzed the immunological activity of this recombinant antigen. The 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 gamma interferon (IFN-{gamma}). Vaccination with HSP60 reduced the fungal burden in mice given 106 or 107 yeasts and protected mice from a lethal challenge. The efficacy of the vaccination was blunted by the neutralization of IFN-{gamma}. CD4+ cells were necessary for the efficacy of the vaccination in both the afferent and efferent phases. Thus, we have demonstrated that this immunodominant antigen is a candidate for the development of a vaccine against this fungus.

* Corresponding author. Mailing address: Division of Infectious Diseases, Department of Medicine, 231 Albert Sabin Way, University of Cincinnati, College of Medicine, Cincinnati, OH 45267-0560. Phone: (513) 558-4704. Fax: (513) 558-2089. E-mail: george.deepe{at}uc.edu

{triangledown} Published ahead of print on 14 July 2008.

Editor: A. Casadevall

Infection and Immunity, September 2008, p. 4214-4221, Vol. 76, No. 9
0019-9567/08/$08.00+0     doi:10.1128/IAI.00753-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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