Exploiting Lipids to Develop Anticryptococcal Vaccines
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Purpose of Review
Cryptococcus spp. are responsible for life-threatening infections in humans causing mortality rates of 70% in developing countries. Antifungal therapy to combat cryptococcosis is based on the combination of amphotericin B, azoles, and 5-flucytosine. However, treatment failure is frequently triggered by antifungal resistance, drug-drug interactions, and toxicity. New alternatives to prevent cryptococcosis are imperative. Here, we discuss the roles of lipids in the immunological control of the disease caused by Cryptococcus spp.
Recently, remarkable advances on immunology of fungal infections have been made and a number of studies indicated the potential of vaccine formulations to combat cryptococcosis. New formulations exploiting virulence regulators and genetically modified attenuated strains have been tested. In this context, lipids have emerged as virulence regulators and immunogens to be explored.
Glucosylceramide (GlcCer), sterylglycosides (SGs), and lipid-containing extracellular vesicles have been recently tested in vaccine formulations and their anticryptococcal efficacy was confirmed in vivo. Together, the data discussed here encourage the use of fungal lipids in anticryptococcal vaccinal strategies.
KeywordsCryptococcosis Immunogenic lipids Glucosylceramide Sterylglycosides Extracellular vesicles Antifungal vaccine
LN was supported by grants from the Brazilian agencies Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq; 408711/2016-7 and 311179/2017-7), Fundação de Amparo e Pesquisa do Estado do Rio de Janeiro (FAPERJ; E-26/202.809/2018-238586). MLR, who is currently on leave from the position of Associate Professor at the Microbiology Institute of the Federal University of Rio de Janeiro (Brazil), is supported by CNPq grants 405520/2018-2, 440015/2018-9, and 301304/2017-3, in addition to Fiocruz grants VPPCB-007-FIO-18 and VPPIS-001-FIO18). MLR is further supported by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, Finance Code 001) and the Instituto Nacional de Ciência e Tecnologia de Inovação em Doenças de Populações Negligenciadas (INCT-IDPN). MDP is supported by NIH grants AI116420, AI125770, AI136934, AI127704, and AI134428 and by the Merit Review Grant I01BX002624 from the Veterans Affairs Medical Center.
Compliance with Ethical Standards
Conflict of Interest
Leonardo Nimrichter and Marcio L. Rodrigues declare no conflict of interest. Dr. Maurizio Del Poeta is the co-founder and Chief Scientific Officer (CSO) of MicroRid Technologies Inc. MLR is currently in leave from a position of associate professor at the Microbiology Institute of UFRJ.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance ••Of major importance
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