Immunogenicity and Efficacy of Cryptococcus neoformans Capsular Polysaccharide Glucuronoxylomannan Peptide Mimotope-Protein Conjugates in Human Immunoglobulin Transgenic Mice

Robert W. Maitta, Kausik Datta, Andrew Lees, Shelley Sims Belouski, Liise-anne Pirofski

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Peptide mimotopes of capsular polysaccharides have been proposed as antigens for vaccines against encapsulated pathogens. In this study, we determined the antibody response to and efficacy of P13, a peptide mimetic of the Cryptococcus neoformans capsular polysaccharide glucuronoxylomannan (GXM), in mice that produce human antibodies. P13 was conjugated to tetanus toxoid (TT) or diphtheria toxoid (DT) and administered subcutaneously in Alhydrogel with or without CpG to mice transgenic for human immunoglobulin loci (XenoMouse mice) and expressing either immunoglobulin G2 (IgG2) (G2 mice) or IgG4 (G4 mice). Mice were vaccinated and revaccinated two or three times. The serum antibody responses of the mice to GXM and P13 and antibody idiotype expression were analyzed by an enzyme-linked immunosorbent assay. The results showed that both P13-TT and P13-DT were antigenic, inducing a mimetic response to P13 in both G2 and G4 mice, and immunogenic, inducing a mimotope response including V H3 (idiotype)-positive antibodies to GXM in G2 but not G4 mice. CpG led to higher titers of IgG to P13 and GXM in P13-TT-vaccinated G2 mice. C. neoformans challenge of P13-protein conjugate-vaccinated and control G2 mice induced anamnestic IgG- and VH3-positive responses to GXM and was associated with a significantly decreased risk of death and a prolongation of survival in P13-DT-vaccinated mice compared to phosphate-buffered saline-treated or protein carrier-vaccinated mice. These findings reveal that P13 elicited a human antibody response with VH3 expression in human immunoglobulin transgenic mice that has been observed for human antibodies to GXM and support the concept that peptide mimotope-based vaccines may hold promise for the treatment of C. neoformans infections.

Original languageEnglish (US)
Pages (from-to)196-208
Number of pages13
JournalInfection and Immunity
Volume72
Issue number1
DOIs
StatePublished - Jan 2004

Fingerprint

Cryptococcus neoformans
Transgenic Mice
Immunoglobulins
Proteins
Diphtheria Toxoid
Tetanus Toxoid
Antibody Formation
Antibodies
Immunoglobulin G
Peptides
Polysaccharides
polysaccharide peptide
glucuronoxylomannan
Vaccines
Aluminum Hydroxide
Carrier Proteins
Enzyme-Linked Immunosorbent Assay
Phosphates

ASJC Scopus subject areas

  • Immunology

Cite this

Immunogenicity and Efficacy of Cryptococcus neoformans Capsular Polysaccharide Glucuronoxylomannan Peptide Mimotope-Protein Conjugates in Human Immunoglobulin Transgenic Mice. / Maitta, Robert W.; Datta, Kausik; Lees, Andrew; Belouski, Shelley Sims; Pirofski, Liise-anne.

In: Infection and Immunity, Vol. 72, No. 1, 01.2004, p. 196-208.

Research output: Contribution to journalArticle

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