Preclinical efficacy of a glucuronoxylomannan-tetanus toxoid conjugate vaccine of Cryptococcus neoformans in a murine model.
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.
Devi
S J
SJ
Laboratory of Developmental and Molecular Immunity, National Institute of Child Health and Human Development, Bethesda, MD 20892, USA.
D000818:Animals; D003455:Cryptococcus neoformans / Q000276:immunology*; D004353:Drug Evaluation, Preclinical; D005657:Fungal Vaccines / Q000032:analysis*; D051379:Mice; D011134:Polysaccharides / Q000378:metabolism*; D013745:Tetanus Toxoid / Q000378:metabolism*; D014614:Vaccines, Synthetic / Q000032:analysis*
D005657:Fungal Vaccines; D011134:Polysaccharides; D013745:Tetanus Toxoid; D014614:Vaccines, Synthetic; C027478:glucuronoxylomannan