This Article Full Text (PDF) Other Versions of this Article: CVI.00130-08v1 15/8/1176    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Google Scholar Articles by Datta, K. Articles by Pirofski, L.-a. PubMed PubMed Citation Articles by Datta, K. Articles by Pirofski, L.-a.

 Previous Article  |  Next Article 

Clin. Vaccine Immunol. doi:10.1128/CVI.00130-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Therapeutic Efficacy of a Conjugate Vaccine containing a Peptide Mimotope of the Cryptococcal Capsular Polysaccharide Glucuronoxylomannan (GXM)

Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461; Biosynexus Inc., 9119 Gaither Road, Gaithersburg, MD 20877; Department of Medicine, and Microbiology & Immunology, Albert Einstein College of Medicine, Bronx, NY 10461

^* To whom correspondence should be addressed. Email: pirofski{at}aecom.yu.edu.

	Abstract

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 vs. C57BL/6), the carrier protein (tetanus toxoid vs. diphtheria toxoid) and the route of infection (intraperitoneal vs. intravenous). Serum GXM levels were correlated with day of death, but the correlation was driven by the carrier protein and mouse strain. 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. Measurement of peripheral blood cytokine (IFN, IL10 and IL6) gene expression showed that P13-conjugate vaccinated Balb/c and C57BL/6 mice mounted a Th2 (IL10)- relative to 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 natural immune response of the host.