Therapeutic potential of antiidiotypic single chain antibodies with yeast killer toxin activity

Magliani, Walter; Conti, Stefania; Bernardis, Flavia De; Gerloni, Mara; Bertolotti, Daniela; Mozzoni, Paola; Cassone, Antonio; Polonelli, Luciano

doi:10.1038/nbt0297-155

Cited by 126 publications

(116 citation statements)

References 22 publications

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“…On closer examination, however, in at least one case, T H 2-derived antibodies have a protective effect by somehow augmenting cell-mediated immunity 39 . In other cases, antibodies can function as opsonins, promoting fungal ingestion and even killing by phagocytes, and several antibodies are directly fungicidal [40][41][42][43][44][45][46][47] (TABLE 1). These kinds of activities are complementary, rather than exclusive, to cell-mediated mechanisms.…”

Section: Evidence For Protective Antibodies Against Fungal Diseasementioning

confidence: 99%

Advances in combating fungal diseases: vaccines on the threshold

2006

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The dramatic increase in fungal diseases in recent years can be attributed to the increased aggressiveness of medical therapy and other human activities. Immunosuppressed patients are at risk of contracting fungal diseases in healthcare settings and from natural environments. Increased prescribing of antifungals has led to the emergence of resistant fungi, resulting in treatment challenges. These concerns, together with the elucidation of the mechanisms of protective immunity against fungal diseases, have renewed interest in the development of vaccines against the mycoses. Most research has used murine models of human disease and, as we review in this article, the knowledge gained from these studies has advanced to the point where the development of vaccines targeting human fungal pathogens is now a realistic and achievable goal.For many years, the concept of developing vaccines against fungal diseases attracted little interest, but this has changed in the past fifteen years (reviewed in REFS 1-6 ) because of the dramatic increase in the incidence rates of fungal diseases worldwide. Carbohydrate and, especially, protein antigens that exert protective immunity against various fungal diseases have now been identified. Fungal carbohydrates can induce the production of antibodies that enhance host resistance in many ways and, fuelled by advances in cellular and molecular biology, numerous fungal proteins that trigger T-cell-mediated immunity and that are immunogenic in murine models of fungal disease have been identified (TABLE 1). A vaccine based on one or more of these candidate antigens could prevent disease by inducing protective antibodies, T-cell-mediated immunity or a combination of both of these aspects of the host immune response. In this Review, we will assess the state of fungal vaccine development, both prophylactic and therapeutic. Overview of the immune response to fungiSuccessful resolution of the diseases caused by pathogenic fungi is crucially dependent on the coordinated interactions of many constituents of the host immune response. The host response to these organisms varies, as would be expected for such a heterogeneous group of pathogens, which differ morphologically, genetically and biochemically. Therefore, the effector molecules and cells that are important for combating opportunistic fungi such as Candida and Aspergillus spp. are less important for primary pathogens such as Coccidioides spp. and Histoplasma capsulatum (BOX 1). The innate response to fungiAs with all pathogens, the innate immune system is a crucial determinant in the antifungal response (FIG. 1) The non-cellular effectors of innate immunity comprise collectins, complement and natural antibodies. These molecules mediate opsonization and therefore promote the ingestion of fungi by phagocytes. One member of the collectin family, pentraxin 3, is necessary for the response to Aspergillus spp. 23 , and the pulmonary collectins surfactant proteins A and D not only cause aggregation of fungi but also have fungicidal activity ...

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Section: Evidence For Protective Antibodies Against Fungal Diseasementioning

confidence: 99%

Advances in combating fungal diseases: vaccines on the threshold

2006

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“…The Totiviridae family is composed by four genera whose members have non-segmented dsRNA genomes, encapsidated in isometric virions called Virus-Like Particles (VLPs), which have no lipids or carbohydrates [1,2]. The virus L-A (ScV-L-A) of Saccharomyces cerevisiae is the type species of genus Totivirus and is one of the most studied mycovirus.…”

Section: Introductionmentioning

confidence: 99%

Characterization of virus-like particles and identification of capsid proteins in Xanthophyllomyces dendrorhous

et al. 2015

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Two dsRNAs of estimated lengths of 5 (L1) and 3.7 (L2) kpb are commonly found in strains of the basidiomycetous yeast Xanthophyllomyces dendrorhous, and the presence of virus-like particles (VLPs) have been described in some strains. Recently, two putative totiviruses (XdV-L1A and XdV-L1B) were identified from L1 dsRNA and one (XdV-L2) from L2 dsRNA in the strain UCD 67-385. In some strains, there are smaller dsRNAs (0.9-1.4 kb) that probable are satellite elements. In this work, the VLPs from several strains of X. dendrorhous, which differ in their dsRNAs content, were separated by sucrose gradient and characterized in relation to the dsRNAs and proteins that compose them. It was found that all types of dsRNAs were encapsidated into VLPs, supporting the hypothesis that the smaller dsRNAs are satellite molecules. A main protein of approx. 76 or 37 kDa composed the virions that only have the L1-dsRNA or L2-dsRNA, respectively. In the strain UCD 67-385, these both proteins were identified as viral capsid protein (CP), allow to confirm the gag predicted ORFs in XdV-L1A, XdV-L1B, and XdV-L2, with CPs of 76.6, 76.2, and 38.8 kDa, respectively. Analysis of predicted structures of CPs of XdV-L1A and XdV-L1B, showed high similitudes with the CPs of ScV-L-A and other totiviruses.

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“…Therefore, based on this report, it might be concluded that younger patients probably benefit from IVIg therapy. Also modifications in the immune system due to previous drugs/therapies in adult patients might influence the [148]. A decapeptide resulting from the variable region sequence and containing part of the CDR1 segment of the KT-scFv light chain also exerted therapeutic activity against experimental mucosal and systemic candidiasis [149].…”

Section: Role Of Antibodies In the Protection Against Fungal Infectiomentioning

confidence: 99%

The protective role of immunoglobulins in fungal infections and inflammation

2014

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International audienceIncreased incidence of fungal infections in the immunocompromised individuals and fungi-mediated allergy and inflammatory conditions in immunocompetent individuals is a cause of concern. Consequently, there is a need for efficient therapeutic alternatives to treat fungal infections and inflammation. Several studies have demonstrated that antibodies or immunoglobulins have a role in restricting the fungal burden and their clearance. However, based on the data from monoclonal antibodies, it is now evident that the efficacy of antibodies in fungal infections is dependent on epitope specificity, abundance of protective antibodies, and their isotype. Antibodies confer protection against fungal infections by multiple mechanisms that include direct neutralization of fungi and their antigens, inhibition of growth of fungi, modification of gene expression, signaling and lipid metabolism, causing iron starvation, inhibition of polysaccharide release, and biofilm formation. Antibodies promote opsonization of fungi and their phagocytosis, complement activation, and antibody-dependent cell toxicity. Passive administration of specific protective monoclonal antibodies could also prove to be beneficial in drug resistance cases, to reduce the dosage and associated toxic symptoms of anti-fungal drugs. The longer half-life of the antibodies and flexibilities to modify their structure/forms are additional advantages. The clinical data obtained with two monoclonal antibodies should incite interests in translating pre-clinical success into the clinics. The anti-inflammatory and immunoregulatory role of antibodies in fungal inflammation could be exploited by intravenous immunoglobulin or IVIg

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Therapeutic potential of antiidiotypic single chain antibodies with yeast killer toxin activity

Cited by 126 publications

References 22 publications

Advances in combating fungal diseases: vaccines on the threshold

Advances in combating fungal diseases: vaccines on the threshold

Characterization of virus-like particles and identification of capsid proteins in Xanthophyllomyces dendrorhous

The protective role of immunoglobulins in fungal infections and inflammation

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