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At least 37 records · Page 2Linked to original sources
PubMed2004

Low virulent strains of Candida albicans: unravelling the antigens for a future vaccine.

Several low virulent Candida albicans mutant strains: CM1613 (deleted in the Mitogen Activated Protein (MAP) Kinase MKC1), CNC13 (deleted in the MAP-kinase HOG1) and the morphological mutant 92' were used as vaccines employing a murine model of systemic candidiasis. In this vaccination trial, only the CNC13 strain was able to induce protection against a subsequent infection with a lethal dose of the wild-type strain. The protection induced by CNC13 vaccinated animals resulted in 60-70% percent of survival. These results demonstrate that collaboration between cellular and humoral responses, induced by the CNC13 mutant, elicited a long lasting and effective protection. Using a proteomic approach (two-dimensional gel electrophoresis followed by Western blotting), twenty-five C. albicans immunogenic proteins were detected and identified by matrix-assisted laser desorption/ionization and/or tandem mass spectrometry. We were able to define an antibody pattern in the sera from the nonvaccinating strains (92' and CM1613), which was different from the profile detected in the sera from surviving animals (vaccinated with the CNC13 mutant). The utility of this proteomic approach has allowed us to identify antigens that induce protective IgG2a antibody isotype in the sera from vaccinated animals: enolase (Eno1p), pyruvate kinase (Cdc19p), pyruvate decarboxylase (Pdc11p), a component from the 40S ribosomal subunit (Bel1p), triosephosphate isomerase (Tpi1p), DL-glycerol phosphatase (Rhr2p), fructose-bisphosphate aldolase (Fba1p) and two new protective antigens: IMP dehydrogenase (Imh3p), and acetyl-CoA synthetase (Acs2p). The antigenic proteins that promote protective antibodies described in this work are excellent candidates for a future fungal vaccine; their heterologous expression and vaccine design is currently underway.

Animals↗
PubMed2004

Dendritic cell-based vaccination against opportunistic fungi.

Efficient responses to the different forms of fungi require different mechanisms of immunity. Dendritic cells (DCs) are uniquely able to decode the fungus-associated information and translate it in qualitatively different T helper (Th) immune responses, in vitro and in vivo. DCs sense fungi in a morphotype-specific manner, through the engagement of distinct recognition receptors ultimately affecting cytokine production and costimulation. Adoptive transfer of different types of DCs activates protective and non-protective Th cells as well as regulatory T cells and affects the outcome of the infections. DCs transfected with fungal RNA also restore antifungal resistance in hematopoietic transplantation. Thus, the remarkable functional plasticity of DCs in response to fungi can be exploited for the deliberate targeting of cells and pathways of cell-mediated immunity in response to fungal vaccines.

Animals↗
PubMedDate not supplied

[Experimental reactivity and antigenic activity of the bacterial-fungal antigen complexes].

The immunogenic and reactogenic properties of monovaccines prepared from Staphylococcus aureus, S. epidermidis and Candida albicans, as well as those of a associated polyvaccine prepared from these infective agents, were experimentally studied on rabbits. The monovaccines and the associated bacterial-fungal vaccines were found to be safe and faintly reactogenic; in the blood serum of vaccinated rabbits a growth in the titer of agglutinins and its preservation at a high level for 4 months were noted.

Animals↗
PubMed2006

Strategies to enhance immune function in hematopoietic transplantation recipients who have fungal infections.

The challenges in the treatment of systemic fungal infections after HSCT include: (1) changing epidemiology as less drug-susceptible saprophytic fungi are increasingly associated with human disease; (2) the difficulty of early and correct diagnosis, even with the new generation of enzymatic immunoassays; (3) the inability to reduce or eliminate predisposing factors, especially severe immune suppression in most transplant patients with these infections and (4) the uncertain role of antifungal drug combinations and risk of drug antagonism complicating effective empiric-pre-emptive therapy. Current, developing and future immune enhancement strategies including recombinant granulocyte- and granulocyte macrophage-colony stimulating factor (GM-CSF), interferon-gamma (IFN-gamma), adjuvant pro-inflammatory cytokine therapy during mobilized donor granulocyte transfusions, therapeutic potential of pentraxin, adaptive immune transfer and dendritic cell fungal vaccines. Improved understanding of the molecular pathogenesis of fungal infections and of the complexity of host antifungal immune responses has provided the critical information to readdress existing treatment paradigms and further evaluate the role of GM-CSF and IFN-gamma early in the course of therapy against life-threatening fungal infections in high-risk patients following stem cell transplantation.

Antifungal Agents↗
PubMed2002

Dendritic cells pulsed with fungal RNA induce protective immunity to Candida albicans in hematopoietic transplantation.

Immature myeloid dendritic cells (DC) phagocytose yeasts and hyphae of the fungus Candida albicans and induce different Th cell responses to the fungus. Ingestion of yeasts activates DC for production of IL-12 and Th1 priming, while ingestion of hyphae induces IL-4 production and Th2 priming. In vivo, generation of antifungal protective immunity is induced upon injection of DC ex vivo pulsed with Candida yeasts but not hyphae. In the present study we sought to determine the functional activity of DC transfected with yeast or hyphal RNA. It was found that DC, from either spleens or bone marrow, transfected with yeast, but not hyphal, RNA 1) express fungal mannoproteins on their surface; 2) undergo functional maturation, as revealed by the up-regulated expression of MHC class II Ags and costimulatory molecules; 3) produce IL-12 but no IL-4; 4) are capable of inducing Th1-dependent antifungal resistance when delivered s.c. in vivo in nontransplanted mice; and 5) provide protection against the fungus in allogeneic bone marrow-transplanted mice, by accelerating the functional recovery of Candida-specific IFN-gamma-producing CD4(+) donor lymphocytes. These results indicate the efficacy of DC pulsed with Candida yeasts or yeast RNA as fungal vaccines and point to the potential use of RNA-transfected DC as anti-infective vaccines in conditions that negate the use of attenuated microorganisms or in the case of poor availability of protective Ags.

Adoptive Transfer↗
PubMed1990

Management of dermatophyte infections in catteries and multiple-cat households.

Successful elimination of dermatophytosis from cats requires clipping of the haircoat, weekly or twice-weekly antifungal dips, and systemic antifungal therapy. In addition, the environment should be repeatedly decontaminated with an appropriate chemical, for example, household bleach. Successful treatment may take weeks to months depending on the circumstances. Monitoring response to therapy is best done via toothbrush-culturing techniques and inoculation of the bristles onto fungal culture media. Currently, there is no successful fungal vaccine, and prevention of reinfection can be difficult and requires careful quarantine measures.

Animals↗
PubMed1998

Orbital infections and inflammations.

Orbital infections and inflammations present to the clinician with similar findings: periorbital edema, erythema, proptosis, and pain. History and clinical examination determine the work-up required to better define the disease process. Orbital infections continue to be associated primarily with diseases of the paranasal sinuses. Haemophilus influenza type B is no longer a significant pathogen, because of an effective vaccine. Fungal infections extending to the orbit are becoming more frequent due to the prevalence of immunocompromised patients. Orbital inflammations continue to be poorly understood, and an adequate classification scheme does not exist. Corticosteroids continue to be the preferred initial treatment, with the roles of radiation and nonsteroidal antiinflammatory medications to be determined. Specific causes of orbital inflammation such as Wegener granulomatosis must be considered to prevent potentially life-threatening complications.

Cellulitis↗
PubMed2004

Treatment of dermatophytosis in dogs and cats: review of published studies.

The recent literature on the treatment of dermatophytosis in dogs and cats was reviewed. Based upon in vitro studies using isolated infected hairs and controlled or field in vivo studies, the following topical treatments were consistently found to be antifungal (i.e. antidermatophyte): lime sulfur (1:16), 0.2% enilconazole rinses, and a combined 2% miconazole/chlorhexidine shampoo. Animals or hairs were either bathed or rinsed once or twice weekly. Itraconazole, griseofulvin and terbinafine were evaluated in controlled or field studies, most commonly involving cats. Griseofulvin (50 mg kg(-1)) was reported to cure infected animals in 41-70 days. Itraconazole (10 mg kg(-1) once daily or in a combined daily/pulse therapy 10 mg kg(-1) once daily for 28 days and then week on/week off) was reported to cure infected animals in 56-70 days. Low-dose itraconazole (1.5-3.0 mg kg(-1)) in 15-day cycles required 1-3 cycles (15-45 days). Various doses of terbinafine (5-40 mg kg(-1)) were reportedly used to treat dogs or cats. The higher doses of terbinafine (> 20 mg kg(-1)) were required to achieve a mycological cure; the number of treatment days to cure varied from 21 to > 126 days. Lufenuron was reported anecdotally to be an effective cure, however, this was not substantiated in controlled studies. Finally, fungal vaccines were not found to be effective against challenge exposure, however, there is evidence that they may be useful in treatment protocols.

Administration, Cutaneous↗
PubMed2004

Antibody regulation of Tcell immunity: implications for vaccine strategies against intracellular pathogens.

Intracellular microbial pathogens cause a plethora of diseases that pose a huge public health challenge. Efficacious prophylactic vaccines are needed to protect the population from this myriad of infectious diseases. Contemporary approaches to vaccine design are guided by the immunobiological paradigm that extracellular pathogens are controlled principally by humoral immunity, involving specific antibodies, whereas host protection against intracellular pathogens requires effectors of cell-mediated immunity. However, this distinct T-helper (Th) type 1 and 2 paradigm of host defense has encountered a major challenge due to the reality that most antigens or vaccines induce mixed immune responses comprising of both humoral and CMI effectors. Besides, the true functional independence of antibodies and T-cells under in vivo physiologic conditions is uncertain. Recent findings have revealed that antibodies exert a significant immunoregulatory effect on T-cell immunity. Thus, a robust and protective T-cell memory response against microbial pathogens such as Chlamydia and Mycobacteria require an effective primary humoral immune response characterized by specific antibody isotypes whose role is to modulate Th1 activation via Fc receptors (FcR) by facilitating a rapid uptake, processing and presentation of pathogen-derived antigens for an enhanced T-cell response. These findings have crystallized into a paradigm shift in host defense wherein different components of the apparently disparate mixed immune responses elicited against a microbial pathogen function concertedly to maximize the principal effector mechanism. This review focuses on the essential role of both arms of the immune system in controlling intracellular microbial pathogens, especially the regulatory role of FcR-mediated antibody function in optimizing the induction of a protective Th1 response. The immunobiological implications are discussed in the context of vaccine design, delivery and evaluation against intracellular microbial pathogens of bacteria, fungi and parasitic origin.

Animals↗
PubMed2002

Induced humoral immunity and vaccination against major human fungal pathogens.

Protection against fungal pathogens can theoretically be elicited by vaccines that stimulate humoral or cellular immunity, or both. There is conclusive evidence that humoral immunity can modify the course of infection against certain pathogenic fungi such as Candida albicans and Cryptococcus neoformans. However, for other fungi, such as Aspergillus fumigatus, the notion that humoral immunity contributes to host defence is unproven. Attempts to evaluate the potential efficacy of humoral immunity using immune sera are often inconclusive, whereas consistent results can be obtained with monoclonal antibodies. Protective monoclonal antibodies can be used to identify antigens that induce useful humoral responses.

Animals↗
PubMed2005

Synthesis and immunological studies of glycoconjugates of Cryptococcus neoformans capsular glucuronoxylomannan oligosaccharide structures.

Antibodies to the glucuronoxylomannan (GXM) component of the polysaccharide capsule of Cryptococcus neoformans are protective and GXM-protein conjugate vaccines can elicit protective immune responses. We report the synthesis of a heptasaccharide oligosaccharide representing the putative dominant motif of serotype A GXM and demonstrate that it is recognized by some monoclonal antibodies (mAbs) generated to GXM. Conjugation of the heptasaccharide to human serum albumin (HSA) resulted in an immunogenic compound that elicited high-titer IgG responses in mice when given with complete Freund's adjuvant. The antibody response elicited by the oligosaccharide conjugate vaccine had characteristics of a T-cell-dependent response. The availability of an immunogenic oligosaccharide representing a structural motif of GXM will prove useful in studies of antibody epitope specificity and represents a potential synthetic oligosaccharide vaccine against this fungal pathogen.

Animals↗
PubMedDate not supplied

Human, monoclonal and recombinant candidacidal, pneumocysticidal and mycobactericidal antibodies.

Antiidiotypic antibodies (antiIds) representing the internal image of some antigenic deteminants have been proposed as surrogate vaccines or, conjugated with toxins, in the immunotherapy of cancer. Experimental studies on antiidiotypic vaccination against fungal infections have been lacking. A conceptually new model of idiotypic vaccination against fungal infection has been recently developed. The vaccine used is monoclonal antibody that in vitro neutralizes the activity of killer toxin from the yeast, Pichia anomala (KT). This is effective against a wide range of fungal pathogens including Candida albicans and Pneumocystis carinii, and is also active against Mycobacterium tuberculosis. In an experimental mouse model, this vaccination was found to confer significant protection against systemic and mucosal infection with C. albicans. Human recombinant killer toxin antibodies and its synthetic derivatives hold promise of a potentially powerful tool against fungal and mycobacterial infections.

Animals↗
PubMed2002

Molecular approaches to the study of Coccidioides immitis.

The study of the molecular biology of Coccidioides sp. is only just beginning. As the importance of coccidioidomycosis grows as a public health problem, our need for understanding of pathogenesis, immune responses, and improved antifungal therapy also increases in proportion. Tools have now become available to study gene manipulation in this pathogen and this will allow molecular approaches to be used. Genetic experiments will also be accelerated by the availability of the whole coccidioidal genome, expected to be made public in the spring of 2003 (see http://www.tigr.org/tdb/tgi/cigi/GenInfo.html). Thus, there seems to be several reasons to expect considerable progress in the coming years.

Animals↗
PubMed1999

Diversity among wild type and vaccination strains of Trichophyton verrucosum investigated using random amplified polymorphic DNA analysis.

We initially tested 20 primers for their ability to amplify genomic DNA of Trichophyton verrucosum using RAPD. Six of these were selected for further study aimed at discrimination of wild type and vaccination strains of T. verrucosum. The results indicate that RAPD successfully distinguished all strains included in the study. In addition, results of corrected cluster analysis were consistent with the fact that the avirulent vaccination strains (T. verrucosum TV-M9 and T. verrucosum TV-M-130) were prepared by ultraviolet (UV) light induced mutagenesis of the standard wild type strain T. verrucosum Strádznice. No marker for a/virulence was detected. These outcomes suggest new possibilities for epidemiological analyses, for discrimination among different vaccination strains and studies of fungal population in vaccinated/infected hosts.

Animals↗