A Monoclonal Antibody Directed against a<i>Candida albicans</i>Cell Wall Mannoprotein Exerts Three Anti-<i>C. albicans</i>Activities

Moragues, Marı́a D.; Omaetxebarria, Miren Josu; Elguezabal, Natalia; Sevilla, Marı́a Jesús; Conti, Stefania; Polonelli, Luciano; Pontón, José

doi:10.1128/iai.71.9.5273-5279.2003

Cited by 150 publications

(139 citation statements)

References 35 publications

(23 reference statements)

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Section: Discussionmentioning

confidence: 73%

“…Such findings were described for C. albicans [26] and C. neoformans infection [27]. Moragues et al [26] characterized an mAb against a mannoprotein with a mass4200 kDa on the cell wall of C. albicans with direct candidacidal activity. Human antibodies against glucosylceramide from C. neoformans inhibited cell budding and fungal growth probably by interfering with the biosynthesis and organization of the cell-wall polymers [27].…”

Section: Discussionmentioning

confidence: 73%

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Passive immunization with monoclonal antibody against a 70‐kDa putative adhesin of Sporothrix schenckii induces protection in murine sporotrichosis

et al. 2008

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Cell-mediated and innate immunity are considered the most important mechanisms of host defense against fungus infections. However, recent studies demonstrated that specific antibodies show different degrees of protection against mycosis. In a previous study, antigens secreted by Sporothrix schenckii induced a specific humoral response in infected animals, mainly against the 70-kDa molecule, indicating a possible participation of antibodies to this antigen in infection control. In the present study, an IgG1 mAb was produced against a 70-kDa glycoprotein of S. schenckii in order to better understand the effect of passive immunization of mice infected with S. schenckii. Results showed a significant reduction in the number of CFU in organs of mice when the mAb was injected before and during S. schenckii infection. Similar results were observed when T-cell-deficient mice were used. Moreover, in a second schedule treatment, the mAb was injected after infection was established, and again we observed a significant reduction in CFU associated with an increase of IFN-cproduction. Also, the 70-kDa antigen is shown to be a putative adhesin present on the surface of this fungus. In conclusion, we report for the first time the protective effect of a specific antibody against S. schenckii.Key words: Adhesins . Mab . Passive immunization . Sporothrix schenckii . Sporotrichosis IntroductionSporotrichosis is a chronic subcutaneous mycosis that occurs worldwide. However, this disease is commonly seen in tropical and subtropical regions [1]. It is caused by traumatic inoculation of the dimorphic fungus Sporothrix schenckii, which is an ubiquitous environmental saprophyte that can be isolated from soil and plant debris [2]. In the past, infections were limited to the cutaneous forms of the disease.Recently, occurrences of more severe clinical forms of this mycosis were described, especially among immunocompromised individuals [3,4].The immunological mechanisms involved in prevention and control of sporotrichosis suggest that cell-mediated immunity plays an important role in protecting The host against S. schenckii [5]. In experimental infections, athymic nude mice are more susceptible to sporotrichosis, and acquired immunity against S. schenckii is mainly mediated by T-cell-activated macrophages [6,7].In contrast, the role of the humoral immune response in protection against this fungus has not been studied in detail. In a previous study, we showed that antigens secreted by S. 3080induce a specific humoral response in infected animals, mainly against the 70-kDa molecule, indicating a possible participation of specific antibodies to this molecule in infection control [8].Cell-mediated and innate immunity are considered the most important mechanisms of host defense against fungus infections. However, recent studies demonstrated that antibodies with defined specificity show different degrees of protection against mycosis [9]. Administration of mAb-mediated protection against Paracoccidioides brasiliensis and Candida albicans and modif...

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Section: Discussionmentioning

confidence: 73%

Section: Discussionmentioning

confidence: 73%

Passive immunization with monoclonal antibody against a 70‐kDa putative adhesin of Sporothrix schenckii induces protection in murine sporotrichosis

et al. 2008

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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%

“…The monoclonal antibody C7 (REF. 44) protects mice against candidiasis 80 apparently by mechanisms similar to antibodies specific for anti-mannotriose. In addition, however, C7 directly inhibits the growth of C. albicans, but by unknown mechanisms 44 .…”

Section: Mechanisms Of Antibody Protectionmentioning

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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“…An IgM MAb C7 that reacts with Als3p and enolase of C. albicans cell wall exerted three anti-candida actions such as candidacidal activity and inhibition of both adhesion and filamentation [77]. Subsequently it was found that the candidacidal activity of this MAb was linked to interference with iron acquisition by C. albicans [78] (Fig.…”

Section: Demonstration Of Protective Role Of Antibodies In Fungal Infmentioning

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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A Monoclonal Antibody Directed against aCandida albicansCell Wall Mannoprotein Exerts Three Anti-C. albicansActivities

Cited by 150 publications

References 35 publications

Passive immunization with monoclonal antibody against a 70‐kDa putative adhesin of Sporothrix schenckii induces protection in murine sporotrichosis

Passive immunization with monoclonal antibody against a 70‐kDa putative adhesin of Sporothrix schenckii induces protection in murine sporotrichosis

Advances in combating fungal diseases: vaccines on the threshold

The protective role of immunoglobulins in fungal infections and inflammation

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