This Article Full Text Full Text (PDF) 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mansour, M. K. Articles by Levitz, S. M. Search for Related Content PubMed PubMed Citation Articles by Mansour, M. K. Articles by Levitz, S. M.

 Previous Article  |  Next Article 

Infection and Immunity, March 2004, p. 1746-1754, Vol. 72, No. 3
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.3.1746-1754.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Protective Efficacy of Antigenic Fractions in Mouse Models of Cryptococcosis

Departments of Medicine and Microbiology, Boston University School of Medicine, Boston, Massachusetts 02118,¹ Archemix Corporation, Cambridge, Massachusetts 02139²

Received 6 October 2003/ Returned for modification 14 October 2003/ Accepted 31 October 2003

Infections due to the encapsulated fungus Cryptococcus neoformans are a significant cause of morbidity and mortality in patients with impaired T-cell function, particularly those with AIDS. Presumably then, T-cell responses to cryptococcal antigens are critical for protection against this ubiquitous fungus. To test the protective efficacy of these antigens as vaccine candidates, secreted cryptococcal antigens were separated by concanavalin A affinity chromatography into adherent (mannoprotein [MP]) and nonadherent (flowthrough [FT]) fractions, and the fractions were tested in murine models of disseminated cryptococcosis. Compared with adjuvant alone, C57BL/6 mice that received two inoculations of MP and FT exhibited prolonged survival and reduced brain and kidney fungal loads following intravenous challenge with C. neoformans strain B3501. MP-immunized animals had increased brain levels of tumor necrosis factor alpha, gamma interferon, and interleukin-2. Histopathologic examination revealed that compared with organs from mice that received only adjuvant, MP-immunized mice were able to recruit a stronger cellular infiltrate in brain, kidney, and liver in response to cryptococcal infection. Conjugated O-linked glycans were necessary for optimal MP-mediated protection, because chemical O deglycosylation reduced the protective efficacy of MP immunization. FT and MP immunization protected B-cell-deficient, but not T-cell-deficient mice, suggesting that protection was T-cell mediated. CBA/J mice also benefited from immunization with FT and MP, although the benefits were more modest than those seen with C57BL/6 mice. Thus, both MP and FT fractions of C. neoformans contain components that protect mice from disseminated cryptococcosis, and this protection appears to be T-cell mediated.

Editor: T. R. Kozel

This article has been cited by other articles:

• Dan, J. M., Kelly, R. M., Lee, C. K., Levitz, S. M. (2008). Role of the Mannose Receptor in a Murine Model of Cryptococcus neoformans Infection. Infect. Immun. 76: 2362-2367 [Abstract] [Full Text]  
• Zaragoza, O., Alvarez, M., Telzak, A., Rivera, J., Casadevall, A. (2007). The Relative Susceptibility of Mouse Strains to Pulmonary Cryptococcus neoformans Infection Is Associated with Pleiotropic Differences in the Immune Response. Infect. Immun. 75: 2729-2739 [Abstract] [Full Text]  
• Martinez, L. R., Casadevall, A. (2006). Cryptococcus neoformans Cells in Biofilms Are Less Susceptible than Planktonic Cells to Antimicrobial Molecules Produced by the Innate Immune System.. Infect. Immun. 74: 6118-6123 [Abstract] [Full Text]  
• Mansour, M. K., Latz, E., Levitz, S. M. (2006). Cryptococcus neoformans Glycoantigens Are Captured by Multiple Lectin Receptors and Presented by Dendritic Cells.. J. Immunol. 176: 3053-3061 [Abstract] [Full Text]  
• Biondo, C., Messina, L., Bombaci, M., Mancuso, G., Midiri, A., Beninati, C., Cusumano, V., Gerace, E., Papasergi, S., Teti, G. (2005). Characterization of Two Novel Cryptococcal Mannoproteins Recognized by Immune Sera. Infect. Immun. 73: 7348-7355 [Abstract] [Full Text]  
• Yauch, L. E., Mansour, M. K., Shoham, S., Rottman, J. B., Levitz, S. M. (2004). Involvement of CD14, Toll-Like Receptors 2 and 4, and MyD88 in the Host Response to the Fungal Pathogen Cryptococcus neoformans In Vivo. Infect. Immun. 72: 5373-5382 [Abstract] [Full Text]