Fungal vaccines: so needed, so feasible, and yet so far off
Arturo Casadevall
Arturo Casadevall
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Commentary

Fungal vaccines: so needed, so feasible, and yet so far off

Abstract

Invasive fungal infections carry high morbidity and mortality, but there are no fungal vaccines. In this issue of the JCI, Okaa et al. report that endonuclease 2 (Eng2), an antigen shared by the Blastomyces, Histoplasma, and Coccidioides species of fungi, elicits protective immunity in mice against blastomycosis, histoplasmosis, and coccidioidomycosis. These results establish a common antigen that can elicit protection against multiple mycoses, encouraging the development of a pan-fungal vaccine. The road to fungal vaccines is made difficult by the need for effectiveness in immunocompromised individuals, the sporadic nature of fungal disease, and the economics of vaccine development. Despite these hurdles, there is optimism that such vaccines can be developed and perhaps find usefulness as adjuncts to antifungal therapy.

Authors

Arturo Casadevall

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Figure 1

Eng2 elicits protective immunity against multiple pathogenic fungi.

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Eng2 elicits protective immunity against multiple pathogenic fungi. (A) ...
(A) Using a human immune system humanized mouse model, Okaa et al. (3) determined that immunization with the fungal enzyme antigen Eng2 protected against infection by Blastomyces, Coccidioides, or Histoplasma spp., representing three major human mycoses. However, sequence variation in Eng2 prevented cross-species protection. (B) Okaa et al. also identified CD4+ T cell responses to Eng2 in patients who had recently recovered from these three mycoses, supporting the interpretation that recognition of Eng2 can elicit cell-mediated immunity during infection. (C) The findings encourage investigation of a trivalent vaccine strategy targeting Eng2, which could provide pan-fungal protection as a preventative or even therapeutic approach. A therapeutic strategy could particularly benefit immunocompromised individuals for whom fungal infection can pose major risks.