Cryptococcus antigens and immune responses: implications for a vaccine

Abstract

Cryptococcosis is a fungal disease primarily occurring in immunocompromised individuals, such as AIDS patients, and is associated with high morbidity and mortality. However, cryptococcosis can occur within immunocompetent populations as observed during an outbreak in Vancouver Island, British Columbia, Canada, the Pacific Northwest and other regions of the USA and in Mediterranean Europe. Mortality rates due to cryptococcosis have significantly declined in economically developed countries since the widespread implementation of highly active antiretroviral therapy. However, the incidence and mortality of this disease remains high in economically undeveloped areas in Africa and Asia where HIV infections are high and availability of HAART is limited. The continuing AIDS epidemic coupled with the increased usage of immunosuppressive drugs to prevent organ transplant rejection or to treat autoimmune diseases has resulted in an increase in individuals at risk for developing cryptococcosis. The purpose of this review is to discuss the need, challenges and potential for developing vaccines against cryptococcosis.

Keywords::

• Cryptococcosis
• Cryptococcus gattii
• Cryptococcus neoformans
• Cryptococcus vaccine
• fungal antigens
• fungal pathogenesis
• fungal vaccines
• host-fungal interactions
• immunotherapy

Financial & competing interests disclosure

F L Wormley and A K Chaturvedi are supported by the Army Research Office of the Department of Defense under Contract No. W911NF-11-1-0136 and grants RO1 AI071752-05 and R21 AI083718-02 from the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH). The content is solely the responsibility of the authors and does not necessarily represent the official views of the Department of Defense or NIAID of the National Institutes of Health. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• • Vaccines should provide protection against the two predominant causative agents of cryptococcosis (C. neoformans and C. gattii).

• • Immune therapies and/or vaccines designed to prevent cryptococcosis must successfully do so in immunosuppressed patients.

• • Populations that should be targeted for vaccines against cryptococcosis include immunocompromised patients, patients on immunosuppressive therapies, and persons at risk of exposure to C. gattii.

• • Anti-cryptococcal vaccines should prevent reactivation of latent disease without generating an over-exuberant immune response like that observed with immune reconstitution inflammatory syndrome.

• • Choosing Cryptococcus antigens that are conserved among other pathogenic fungi can provide cross-protection against multiple disparate fungal diseases.

• • Optimal vaccine mediated immunity requires the refinement and/or generation of appropriate adjuvants and vaccine delivery platforms.