The common Cryptococcus neoformans glucuronoxylomannan M2 motif elicits non-protective antibodies

Antonio Nakouzi, Tong Zhang, Stefan Oscarson, Arturo Casadevall

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3513-3518
Number of pages6
JournalVaccine
Volume27
Issue number27
DOIs
StatePublished - Jun 2 2009
Externally publishedYes

Keywords

  • Antibody
  • Cryptococcus neoformans
  • Immune response
  • Vaccine

ASJC Scopus subject areas

  • Molecular Medicine
  • General Immunology and Microbiology
  • General Veterinary
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

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