Vaccinations with Recombinant Variants of
            <i>Aspergillus fumigatus</i>
            Allergen Asp f 3 Protect Mice against Invasive Aspergillosis

Ito, James I.; Lyons, Joseph M.; Hong, Teresa; Tamae, Daniel; Liu, Yi-Kuang; Wilczynski, Sharon P.; Kalkum, Markus

doi:10.1128/iai.00815-06

Cited by 91 publications

(102 citation statements)

References 44 publications

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“…By showing their Th2 promoting activity, the present study confirms the allergenic potential of the secreted proteins (12,14). However, the vaccinating potential of some allergens, including secreted proteases (37), have also been described (8,11). Although the secretion of aspartic proteases has long been recognized as a virulence-associated trait of Candida spp.…”

Section: Discussionsupporting

confidence: 55%

Immune Sensing of Aspergillus fumigatus Proteins, Glycolipids, and Polysaccharides and the Impact on Th Immunity and Vaccination

Bozza

Clavaud

Giovannini

et al. 2009

The Journal of Immunology

168

186

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The ability of the fungus Aspergillus fumigatus to activate, suppress, or subvert host immune response during life cycle in vivo through dynamic changing of cell wall structure and secretion implicates discriminative immune sensing of distinct fungal components. In this study, we have comparatively assessed secreted- and membrane-anchored proteins, glycolipids, and polysaccharides for the ability to induce vaccine-dependent protection in transplanted mice and Th cytokine production by human-specific CD4+ T cell clones. The results show that the different fungal components are endowed with the distinct capacity to activate Th cell responses in mice and humans, with secreted proteins inducing Th2 cell activation, membrane proteins Th1/Treg, glycolipids Th17, and polysaccharides mostly IL-10 production. Of interest, the side-by-side comparison revealed that at least three fungal components (a protease and two glycosylphosphatidylinositol-anchored proteins) retained their immunodominant Th1/Treg activating potential from mice to humans. This suggests that the broadness and specificity of human T cell repertoire against the fungus could be selectively exploited with defined immunoactive Aspergillus Ags.

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Section: Discussionsupporting

confidence: 55%

Immune Sensing of Aspergillus fumigatus Proteins, Glycolipids, and Polysaccharides and the Impact on Th Immunity and Vaccination

Bozza

Clavaud

Giovannini

et al. 2009

The Journal of Immunology

168

186

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“…Therefore, previously, we engineered truncated nonallergen versions of rAsp f3 that lacked the IgEbinding epitope and protected immunosuppressed mice against aspergillosis. The rAsp f3 variant that spans residues 15 to 168, Asp f3(15-168), elicited better protection (83%) than full-length rAsp f3(1-168) (25).…”

mentioning

confidence: 99%

“…Asp f3 is a putative peroxisomal protein and was identified as a potential vaccine candidate by mass spectrometric analysis of antigens that bound to antibodies from immunocompetent mice after pulmonary exposure to nonlethal doses of A. fumigatus conidia (25). The Asp f3 protein has also been described as a major allergen.…”

mentioning

confidence: 99%

“…Recently, we showed that immunizations with recombinant Asp f3 (rAsp f3) of A. fumigatus effectively protected CF-1 mice from invasive fungal infections in a corticosteroid model of immunosuppression (25). Asp f3 is a putative peroxisomal protein and was identified as a potential vaccine candidate by mass spectrometric analysis of antigens that bound to antibodies from immunocompetent mice after pulmonary exposure to nonlethal doses of A. fumigatus conidia (25).…”

mentioning

confidence: 99%

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CD4⁺T Cells Mediate the Protective Effect of the Recombinant Asp f3-Based Anti-Aspergillosis Vaccine

et al. 2011

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The mortality and morbidity caused by invasive aspergillosis present a major obstacle to the successful treatment of blood cancers with hematopoietic cell transplants. Patients who receive hematopoietic cell transplants are usually immunosuppressed for extended periods, and infection with the ubiquitous mold Aspergillus fumigatus is responsible for most cases of aspergillosis. Previously, we demonstrated that vaccination with recombinant forms of the A. fumigatus protein Asp f3 protected cortisone acetate-immunosuppressed mice from experimentally induced pulmonary aspergillosis. Here, we investigated the vaccine's protective mechanism and evaluated in particular the roles of antibodies and T cells. After vaccination, Asp f3-specific preinfection IgG titers did not significantly differ between surviving and nonsurviving mice, and passive transfer of anti-Asp f3 antibodies did not protect immunosuppressed recipients from aspergillosis. We experimentally confirmed Asp f3's predicted peroxisomal localization in A. fumigatus hyphae. We found that fungal Asp f3 is inaccessible to antibodies, unless both cell walls and membranes have been permeabilized. Antibodyinduced depletion of CD4 ؉ T cells reduced the survival of recombinant Asp f3 (rAsp f3)-vaccinated mice to nonimmune levels, and transplantation of purified CD4 ؉ T cells from rAsp f3-vaccinated mice into nonimmunized recipients transferred antifungal protection. In addition, residues 60 to 79 and 75 to 94 of Asp f3 contain epitopes that induce proliferation of T cells from vaccinated survivors. Vaccine-primed CD4 ؉ T cells are not expected to clear the fungal pathogen directly; however, they may locally activate immunosuppressed phagocytes that elicit the antifungal effect.

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“…68 The group subsequently reported that sera from the vaccinated animals contained antibodies against Asp f3. 69 The vaccination of Asp f3 was effective to prevent the subsequent Aspergillus infection in corticosteroid-treated mice. CD4…”

Section: Importance Of Immunity Against Aspergillus Infectionsmentioning

confidence: 99%

Immunotherapy for opportunistic infections: Current status and future perspectives

Fuji¹,

Löffler

Einsele

et al. 2016

Virulence

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The outcome after allogeneic haematopoietic stem cell transplantation (allo-HSCT) has significantly improved during the last decades. However, opportunistic infections such as viral and mold infections are still a major obstacle for cure. Within this field, adoptive T cell therapy against pathogens is a promising treatment approach. Recently, the techniques to develop T cell products including pathogen-specific T cells have been sophisticated and are now available in accordance to good manufacturing practice (GMP). Here, we aim to summarize current knowledge about adoptive T cell therapy against viral and mold infections.

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Vaccinations with Recombinant Variants of Aspergillus fumigatus Allergen Asp f 3 Protect Mice against Invasive Aspergillosis

Cited by 91 publications

References 44 publications

Immune Sensing of Aspergillus fumigatus Proteins, Glycolipids, and Polysaccharides and the Impact on Th Immunity and Vaccination

Immune Sensing of Aspergillus fumigatus Proteins, Glycolipids, and Polysaccharides and the Impact on Th Immunity and Vaccination

CD4⁺T Cells Mediate the Protective Effect of the Recombinant Asp f3-Based Anti-Aspergillosis Vaccine

Immunotherapy for opportunistic infections: Current status and future perspectives

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Vaccinations with Recombinant Variants of Aspergillus fumigatus Allergen Asp f 3 Protect Mice against Invasive Aspergillosis

Cited by 91 publications

References 44 publications

Immune Sensing of Aspergillus fumigatus Proteins, Glycolipids, and Polysaccharides and the Impact on Th Immunity and Vaccination

Immune Sensing of Aspergillus fumigatus Proteins, Glycolipids, and Polysaccharides and the Impact on Th Immunity and Vaccination

CD4+T Cells Mediate the Protective Effect of the Recombinant Asp f3-Based Anti-Aspergillosis Vaccine

Immunotherapy for opportunistic infections: Current status and future perspectives

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Product

Resources

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CD4⁺T Cells Mediate the Protective Effect of the Recombinant Asp f3-Based Anti-Aspergillosis Vaccine