Therapeutic efficacy of a conjugate vaccine containing a peptide mimotope of cryptococcal capsular polysaccharide glucuronoxylomannan

Kausik Datta, Andrew Lees, Liise-anne Pirofski

Research output: Contribution to journalArticle

30 Citations (Scopus)

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 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-γ], 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-γ)-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.

Original languageEnglish (US)
Pages (from-to)1176-1187
Number of pages12
JournalClinical and Vaccine Immunology
Volume15
Issue number8
DOIs
StatePublished - Aug 2008

Fingerprint

Conjugate Vaccines
Polysaccharides
Carrier Proteins
Vaccines
Interleukin-10
Peptides
Diphtheria Toxoid
Tetanus Toxoid
Gene expression
Interferons
Interferon-gamma
Interleukin-6
Blood
Therapeutics
Cytokines
Infection
Antibodies
Cryptococcosis
Cryptococcus neoformans
Immunomodulation

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Immunology
  • Immunology and Allergy
  • Microbiology (medical)

Cite this

Therapeutic efficacy of a conjugate vaccine containing a peptide mimotope of cryptococcal capsular polysaccharide glucuronoxylomannan. / Datta, Kausik; Lees, Andrew; Pirofski, Liise-anne.

In: Clinical and Vaccine Immunology, Vol. 15, No. 8, 08.2008, p. 1176-1187.

Research output: Contribution to journalArticle

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