Universal fungal vaccines

Hamad, Mawieh

doi:10.4161/hv.21838

Cited by 11 publications

(4 citation statements)

References 63 publications

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“…As responses to fungi depend on both arms of the immune response, and because such responses are complex, depending on the site of infection (mucosal vs systemic infection) and the type of fungus (e.g., Candida or Cryptococcus vs a mold), much more groundwork needs to be done to decipher the key elements of a successful vaccine. In addition, there are questions regarding the efficacy and feasibility of using a vaccine in immunocompromised patients, since they are incapable of mounting a complete immune response ( 105 ).…”

Section: The Role Of Cd8 + T Cells In the Antifungmentioning

confidence: 99%

Methods of Controlling Invasive Fungal Infections Using CD8+ T Cells

2018

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Invasive fungal infections (IFIs) cause high rates of morbidity and mortality in immunocompromised patients. Pattern-recognition receptors present on the surfaces of innate immune cells recognize fungal pathogens and activate the first line of defense against fungal infection. The second line of defense is the adaptive immune system which involves mainly CD4+ T cells, while CD8+ T cells also play a role. CD8+ T cell-based vaccines designed to prevent IFIs are currently being investigated in clinical trials, their use could play an especially important role in acquired immune deficiency syndrome patients. So far, none of the vaccines used to treat IFI have been approved by the FDA. Here, we review current and future antifungal immunotherapy strategies involving CD8+ T cells. We highlight recent advances in the use of T cells engineered using a Sleeping Beauty vector to treat IFIs. Recent clinical trials using chimeric antigen receptor (CAR) T-cell therapy to treat patients with leukemia have shown very promising results. We hypothesized that CAR T cells could also be used to control IFI. Therefore, we designed a CAR that targets β-glucan, a sugar molecule found in most of the fungal cell walls, using the extracellular domain of Dectin-1, which binds to β-glucan. Mice treated with D-CAR+ T cells displayed reductions in hyphal growth of Aspergillus compared to the untreated group. Patients suffering from IFIs due to primary immunodeficiency, secondary immunodeficiency (e.g., HIV), or hematopoietic transplant patients may benefit from bioengineered CAR T cell therapy.

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Section: The Role Of Cd8 + T Cells In the Antifungmentioning

confidence: 99%

Methods of Controlling Invasive Fungal Infections Using CD8+ T Cells

2018

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“…Although there are diverse variations in polysaccharide composition across species, there are conserved components, such as a core of branched β-1,3-glucan-chitin [24]. Thus, the fact that fungi have preserved compounds in both the cell wall and plasma membrane makes it theoretically possible to develop a universal vaccine, where the presence of a common antigen among closely-related and/or disparate pathogens could be used to protect against different mycosis or even disease caused by others microorganisms [25,26]. For example, a β-glucan laminarin has demonstrated protection against infection by Candida and Aspergillus species by means of growth-inhibiting antibodies, particularly when conjugated with the diphtheria toxoid CRM197 carrier protein [27][28][29].…”

Section: Fungal Vaccine: Some Challengesmentioning

confidence: 99%

Advances in Fungal Peptide Vaccines

Silva

Taborda

Nosanchuk

2020

JoF

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Vaccination is one of the greatest public health achievements in the past century, protecting and improving the quality of life of the population worldwide. However, a safe and effective vaccine for therapeutic or prophylactic treatment of fungal infections is not yet available. The lack of a vaccine for fungi is a problem of increasing importance as the incidence of diverse species, including Paracoccidioides, Aspergillus, Candida, Sporothrix, and Coccidioides, has increased in recent decades and new drug-resistant pathogenic fungi are emerging. In fact, our antifungal armamentarium too frequently fails to effectively control or cure mycoses, leading to high rates of mortality and morbidity. With this in mind, many groups are working towards identifying effective and safe vaccines for fungal pathogens, with a particular focus of generating vaccines that will work in individuals with compromised immunity who bear the major burden of infections from these microbes. In this review, we detail advances in the development of vaccines for pathogenic fungi, and highlight new methodologies using immunoproteomic techniques and bioinformatic tools that have led to new vaccine formulations, like peptide-based vaccines.

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“…Another group of patients that could benefit from fungal vaccination include patients with breaches in their cutaneous or mucosal defenses, bearing permanent central venous catheters, or undergoing long-term hospitalization in intensive care units. Because of the possible side effects associated to the use of these approaches in this setting of patients, vaccine design should consider the nature of the relationship between opportunistic fungi and their human hosts [56]. For example, vaccination against commensals may disrupt the asymptomatic and possibly beneficial relationship between the fungus and its host.…”

Section: Challenges and Opportunities In Fungal Vaccinationmentioning

confidence: 99%

Fungal Vaccines and Immunotherapeutics: Current Concepts and Future Challenges

Carvalho

Duarte-Oliveira

Gonçalves

et al. 2017

Curr Fungal Infect Rep

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Purpose of review The remarkable advances in modern medicine have paradoxically resulted in a rapidly expanding population of immunocompromised patients displaying extreme susceptibility to life-threatening fungal infections. There are currently no licensed vaccines, and the prophylaxis and therapy of fungal infections in at-risk individuals remains challenging, contributing to undesirable mortality and morbidity rates. The design of successful antifungal preventive approaches has been hampered by an insufficient understanding of the dynamics of the host-fungus interaction and the mechanisms that underlie heterogenous immune responses to vaccines and immunotherapy. Recent findings Recent advances in proteomics and glycomics have contributed to the identification of candidate antigens for use in subunit vaccines, novel adjuvants, and delivery systems to boost the efficacy of protective vaccination responses that are becoming available, and several targets are being exploited in immunotherapeutic approaches. Summary We review some of the emerging concepts as well as the inherent challenges to the development of fungal vaccines and immunotherapies to protect at-risk individuals.

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Universal fungal vaccines

Cited by 11 publications

References 63 publications

Methods of Controlling Invasive Fungal Infections Using CD8+ T Cells

Methods of Controlling Invasive Fungal Infections Using CD8+ T Cells

Advances in Fungal Peptide Vaccines

Fungal Vaccines and Immunotherapeutics: Current Concepts and Future Challenges

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