Preclinical efficacy of a glucuronoxylomannan-tetanus toxoid conjugate vaccine of Cryptococcus neoformans in a murine model

Vaccine. 1996 Jun;14(9):841-4. doi: 10.1016/0264-410x(95)00256-z.

Abstract

The encapsulated yeast, Cryptococcus neoformans, causes life-threatening meningoencephalitis in immunocompromised humans, especially in AIDS patients. Fatality and relapse rates remain quite high despite aggressive therapy. A conjugate vaccine composed of the cryptococcal capsular glucuronoxylomannan covalently coupled to tetanus toxoid (GXM-TT) was constructed and evaluated. The vaccine elicited high levels of capsular antibodies in mice by active and passive immunizations and conferred 70-80% protection against a moderate challenge with 10(3) C, neoformans. Monitoring of serum GXM and anti-GXM antibody levels and of incidence of cryptococcal isolation from various organs of mice suggested that presence of vaccine-induced antibodies during the first 4-6 weeks of infection is critical for clearance of cryptococci from various organs, for limiting serum GXM titers from reaching immunosuppressive levels and ultimately for survival. GXM-TT is the first defined fungal vaccine to confer antibody-mediated protection against a systemic mycosis in an animal model. GXM-TT is being evaluated for safety and immunogenicity in healthy and HIV-infected human volunteers at the National Institutes of Health.

Publication types

  • Review

MeSH terms

  • Animals
  • Cryptococcus neoformans / immunology*
  • Drug Evaluation, Preclinical
  • Fungal Vaccines / analysis*
  • Mice
  • Polysaccharides / metabolism*
  • Tetanus Toxoid / metabolism*
  • Vaccines, Synthetic / analysis*

Substances

  • Fungal Vaccines
  • Polysaccharides
  • Tetanus Toxoid
  • Vaccines, Synthetic
  • glucuronoxylomannan