Fungal Vaccines and Immunotherapeutics

Santos, Evelyn; Levitz, Stuart M.

doi:10.1101/cshperspect.a019711

Cited by 28 publications

(22 citation statements)

References 73 publications

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“…Accordingly, researchers have dedicated studies to developing robust, durable and safe fungal vaccines, especially those that may be useful for endemic infections or in chronic or superimposed infections in intensive care patients (Santos and Levitz, 2014; Shahid, 2016). …”

Section: Antifungal Immunotherapy: Vaccinesmentioning

confidence: 99%

Antifungal Therapy: New Advances in the Understanding and Treatment of Mycosis

et al. 2017

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The high rates of morbidity and mortality caused by fungal infections are associated with the current limited antifungal arsenal and the high toxicity of the compounds. Additionally, identifying novel drug targets is challenging because there are many similarities between fungal and human cells. The most common antifungal targets include fungal RNA synthesis and cell wall and membrane components, though new antifungal targets are being investigated. Nonetheless, fungi have developed resistance mechanisms, such as overexpression of eﬄux pump proteins and biofilm formation, emphasizing the importance of understanding these mechanisms. To address these problems, different approaches to preventing and treating fungal diseases are described in this review, with a focus on the resistance mechanisms of fungi, with the goal of developing efficient strategies to overcoming and preventing resistance as well as new advances in antifungal therapy. Due to the limited antifungal arsenal, researchers have sought to improve treatment via different approaches, and the synergistic effect obtained by the combination of antifungals contributes to reducing toxicity and could be an alternative for treatment. Another important issue is the development of new formulations for antifungal agents, and interest in nanoparticles as new types of carriers of antifungal drugs has increased. In addition, modifications to the chemical structures of traditional antifungals have improved their activity and pharmacokinetic parameters. Moreover, a different approach to preventing and treating fungal diseases is immunotherapy, which involves different mechanisms, such as vaccines, activation of the immune response and inducing the production of host antimicrobial molecules. Finally, the use of a mini-host has been encouraging for in vivo testing because these animal models demonstrate a good correlation with the mammalian model; they also increase the speediness of as well as facilitate the preliminary testing of new antifungal agents. In general, many years are required from discovery of a new antifungal to clinical use. However, the development of new antifungal strategies will reduce the therapeutic time and/or increase the quality of life of patients.

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Section: Antifungal Immunotherapy: Vaccinesmentioning

confidence: 99%

Antifungal Therapy: New Advances in the Understanding and Treatment of Mycosis

et al. 2017

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“…The GP vaccine platform has been previously investigated primarily in the context of developing fungal vaccines [ 28 , 67 ] due to the lack of effective vaccines for fungal infections. Fungi resist lysis by the complement system, but the deposition of iC3b on a fungus prompts opsonization and phagocytosis [ 68 ]. In many cases, antibodies are not protective against fungal infections [ 69 ], and some vaccines are now focusing on producing cellular immune responses as well [ 28 ] given that T cells are major players in fighting fungal infections.…”

Section: Discussionmentioning

confidence: 99%

Harnessing antifungal immunity in pursuit of a Staphylococcus aureus vaccine strategy

et al. 2020

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Staphylococcus aureus ( S . aureus ) is one of the most common bacterial infections worldwide, and antibiotic resistant strains such as Methicillin-Resistant S . aureus (MRSA) are a major threat and burden to public health. MRSA not only infects immunocompromised patients but also healthy individuals and has rapidly spread from the healthcare setting to the outside community. However, all vaccines tested in clinical trials to date have failed. Immunocompromised individuals such as patients with HIV or decreased levels of CD4 + T cells are highly susceptible to S . aureus infections, and they are also at increased risk of developing fungal infections. We therefore wondered whether stimulation of antifungal immunity might promote the type of immune responses needed for effective host defense against S . aureus . Here we show that vaccination of mice with a fungal β-glucan particle (GP) loaded with S . aureus antigens provides protective immunity to S . aureus . We generated glucan particles loaded with the four S . aureus proteins ClfA, IsdA, MntC, and SdrE, creating the 4X-SA-GP vaccine. Vaccination of mice with three doses of 4X-SA-GP promoted protection in a systemic model of S . aureus infection with a significant reduction in the bacterial burden in the spleen and kidneys. 4X-SA-GP vaccination induced antigen-specific Th1 and Th17 CD4 + T cell and antibody responses and provided long-term protection. This work suggests that the GP vaccine system has potential as a novel approach to developing vaccines for S . aureus .

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“…The key protection lies in the ability of vaccines to boost host immunity, including pro-inflammatory, cell-mediated, Th1 or Th17 responses to enhance phagocytic killing of the fungus [ 103 ]. Dedicated studies have been conducted by researchers in recent years to develop safe and effective fungal vaccines [ 104 , 105 ]. Though no specific vaccine has been developed to prevent Candida biofilms, however, two promising fungal vaccines against invasive candidiasis have been developed and they are currently under clinical trials.…”

Section: Future Directions Of Research On New Antifungal Drugs Tarmentioning

confidence: 99%

Transcriptomic and Genomic Approaches for Unravelling Candida albicans Biofilm Formation and Drug Resistance—An Update

Chong

Chin

Wong

et al. 2018

Genes

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Candida albicans is an opportunistic fungal pathogen, which causes a plethora of superficial, as well as invasive, infections in humans. The ability of this fungus in switching from commensalism to active infection is attributed to its many virulence traits. Biofilm formation is a key process, which allows the fungus to adhere to and proliferate on medically implanted devices as well as host tissue and cause serious life-threatening infections. Biofilms are complex communities of filamentous and yeast cells surrounded by an extracellular matrix that confers an enhanced degree of resistance to antifungal drugs. Moreover, the extensive plasticity of the C. albicans genome has given this versatile fungus the added advantage of microevolution and adaptation to thrive within the unique environmental niches within the host. To combat these challenges in dealing with C. albicans infections, it is imperative that we target specifically the molecular pathways involved in biofilm formation as well as drug resistance. With the advent of the -omics era and whole genome sequencing platforms, novel pathways and genes involved in the pathogenesis of the fungus have been unraveled. Researchers have used a myriad of strategies including transcriptome analysis for C. albicans cells grown in different environments, whole genome sequencing of different strains, functional genomics approaches to identify critical regulatory genes, as well as comparative genomics analysis between C. albicans and its closely related, much less virulent relative, C. dubliniensis, in the quest to increase our understanding of the mechanisms underlying the success of C. albicans as a major fungal pathogen. This review attempts to summarize the most recent advancements in the field of biofilm and antifungal resistance research and offers suggestions for future directions in therapeutics development.

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Fungal Vaccines and Immunotherapeutics

Cited by 28 publications

References 73 publications

Antifungal Therapy: New Advances in the Understanding and Treatment of Mycosis

Antifungal Therapy: New Advances in the Understanding and Treatment of Mycosis

Harnessing antifungal immunity in pursuit of a Staphylococcus aureus vaccine strategy

Transcriptomic and Genomic Approaches for Unravelling Candida albicans Biofilm Formation and Drug Resistance—An Update

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