The Cryptococcus neoformans capsular glucuronoxylomannan (GXM) is a potential vaccine antigen that can elicit protective and non-protective antibodies. In an attempt to focus the immune response on a single antigenic component, a heptasaccharide oligosaccharide representing the major structural motif (M2) of the most common clinical isolate was synthesized and conjugated to human serum albumin (HSA). Monoclonal antibodies (mAbs) generated from mice immunized with M2–HSA produced the characteristic punctuate immunofluorescence associated with non-protective mAbs. None of the mAbs elicited by M2 immunization was opsonic. Passive administration of mAbs elicited by M2–HSA was not protective and there was no difference in the survival of mice immunized with M2–HSA and HSA. Hence, we conclude that the M2 motif represents an antigenic determinant in C. neoformans GXM that elicits non-protective responses and is not a suitable vaccine candidate. Furthermore, the results illustrate the first molecular assignment of a C. neoformans polysaccharide epitope and suggest a general strategy for the identification of GXM epitopes.
antibody, vaccine, immune response, Cryptococcus neoformans
NCBI PubMed ID: 19464529Publication DOI: 10.1016/j.vaccine.2009.03.089Journal NLM ID: 8406899Publisher: Elsevier
Correspondence: casadeva@aecom.yu.edu (A. Casadevall)
Institutions: Centre for Synthesis and Chemical Biology, UCD School of Chemistry and Chemical Biology, University College Dublin, Belfield, Dublin 4, Ireland, Department of Microbiology and Immunology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, Department of Medicine (Division of Infectious Diseases), Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461
Methods: DNA sequencing, ELISA, serological methods, statistical analysis, immunization, phagocytosis assay, immunofluorescence analysis
Found