A Call to Arms: Quest for a Cryptococcal Vaccine

• Published in: Trends in microbiology (Regular ed.) Vol. 26; no. 5; pp. 436 - 446
• Main Authors: Caballero Van Dyke, Marley C., Wormley, Floyd L.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.05.2018; Elsevier Science Ltd
• Subjects: Acquired immune deficiency syndrome; AIDS; Animals; Antigens, Fungal - immunology; cryptococcal vaccine; Cryptococcosis; Cryptococcosis - immunology; Cryptococcosis - prevention & control; Cryptococcus; Cryptococcus gattii; Cryptococcus gattii - immunology; Cryptococcus gattii - pathogenicity; Cryptococcus neoformans; Cryptococcus neoformans - immunology; Cryptococcus neoformans - pathogenicity; Disease Models, Animal; Disease prevention; Fungal infections; Fungal Proteins - immunology; Fungal Vaccines; Fungi; Glycolipids - immunology; Humans; Investment; Literature reviews; Morbidity; R&D; Recombinant Proteins - immunology; Research & development; Vaccination; Vaccines; Vaccines, Attenuated - immunology; Vaccines, Inactivated - immunology; Vaccines, Synthetic - immunology; Cryptococcus gattii; Cryptococcus; cryptococcal vaccine; Cryptococcus neoformans; cryptococcosis
• ISSN: 0966-842X; 1878-4380
• DOI: 10.1016/j.tim.2017.10.002

Cryptococcosis remains a significant cause of morbidity and mortality world-wide, particularly among AIDS patients. Yet, to date, there are no licensed vaccines clinically available to treat or prevent cryptococcosis. In this review, we provide a rationale to support continued investment in Cryptococcus vaccine research, potential challenges that must be overcome along the way, and a literature review of the current progress underway towards developing a vaccine to prevent cryptococcosis. Expansion of Cryptococcus in unique patient populations and environmental niches highlights the need for a prophylactic vaccine to prevent cryptococcosis caused by virulent C. neoformans and C. gattii. Vaccination with heat-killed Cryptococcus mutants containing cell-wall modifications appears to induce protective immune responses against cryptococcosis in mice. Experimental studies show potential for eliciting long-lasting protective immunity against cryptococcosis in CD4+ T cell-deficient hosts. Administration of fungal glycolipids, such as glucosylceramide, demonstrates significant protection against subsequent Cryptococcus infection in mice. Mice vaccinated with an innovative β-glucan antigen-delivery platform containing immune stimulatory Cryptococcus fractions have protective anticryptococcal immune responses against virulent strains of C. neoformans and C. gattii.