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Clinical and Vaccine Immunology, August 2008, p. 1176-1187, Vol. 15, No. 8
1071-412X/08/$08.00+0 doi:10.1128/CVI.00130-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.
Therapeutic Efficacy of a Conjugate Vaccine Containing a Peptide Mimotope of Cryptococcal Capsular Polysaccharide Glucuronoxylomannan
Kausik Datta,1,
Andrew Lees,2,
and
Liise-anne Pirofski1,3*
Department of Microbiology and Immunology,1 Department of Medicine, Albert Einstein College of Medicine, Bronx, New York 10461,3 Biosynexus Inc., 9119 Gaither Road, Gaithersburg, Maryland 208772
Received 12 April 2008/ Returned for modification 8 May 2008/ Accepted 27 May 2008
Vaccination with P13, a peptide mimotope of the cryptococcal capsular polysaccharide glucuronoxylomannan (GXM), has been shown to confer protection against a subsequent lethal Cryptococcus neoformans challenge. In this study, we sought to investigate whether P13-based vaccines could be effective in an already-established infection. To address this question, we developed a systemic chronic cryptococcal infection model. We vaccinated chronically infected mice with P13-protein conjugates and monitored their survival. Compared to the controls, the conjugates prolonged the survival of chronically infected mice. The degree of protection was a function of the mouse strain (BALB/c or C57BL/6), the carrier protein (tetanus toxoid or diphtheria toxoid), and the route of infection (intraperitoneal or intravenous). Serum GXM levels were correlated with the day of death, but the correlation was driven by the carrier protein and mouse strain. The passive transfer of heat-treated sera from P13 conjugate-vaccinated mice conferred protection to naïve BALB/c mice, indicating that antibody immunity could contribute to protection. The measurement of peripheral blood cytokine (gamma interferon [IFN-
], interleukin-10 [IL-10], and IL-6) gene expression showed that P13 conjugate-vaccinated BALB/c and C57BL/6 mice mounted a strong Th2 (IL-10)-like response relative to the Th1 (IFN-)-like response, with the degree depending on the mouse strain and carrier protein. Taken together, our data suggest that a vaccine could hold promise in the setting of chronic cryptococcosis, and that vaccine efficacy could depend on immunomodulation and augmentation of the natural immune response of the host.
* Corresponding author. Mailing address: Albert Einstein College of Medicine, Medicine/Infectious Diseases, 1300 Morris Park Ave., Room 709, Forchheimer Bldg., Bronx, NY 10461. Phone: (718) 430-2372. Fax: (718) 430-8968. E-mail: pirofski{at}aecom.yu.edu
Published ahead of print on 4 June 2008.
Present address: Oregon Health & Science University, HRC-330A (Mailcode: L-457), 3181 Sam Jackson Park Road, Portland, OR 97239.
Present address: Fina BioSolutions LLC, 9610 Medical Center Dr., Suite 200, Rockville, MD 20850.
Clinical and Vaccine Immunology, August 2008, p. 1176-1187, Vol. 15, No. 8
1071-412X/08/$08.00+0 doi:10.1128/CVI.00130-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.
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