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Monoclonal Antibodies as Tools to Diagnose and Treat Fungal Infection
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Monoclonal Antibodies as Tools to Diagnose and Treat Fungal Infection

A special issue of Journal of Fungi (ISSN 2309-608X). This special issue belongs to the section "Fungal Pathogenesis and Disease Control".

Deadline for manuscript submissions: closed (15 June 2021) | Viewed by 14226

Special Issue Editors

Prof. Dr. Frank Ebel

E-Mail Website
Guest Editor
Institute for Infectious Diseases and Zoonoses, Ludwig-Maximilians-University of Munich, Munich, Germany
Interests: mycology; microbiology; immunology
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Carlos Pelleschi Taborda

E-Mail Website
Guest Editor
Laboratory of Pathogenic Dimorphic Fungi, Departamento de Microbiologia, University of São Paulo, São Paulo, Brazil
Interests: medical mycology; parasite–host relationship; systemic and emerging mycoses
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Invasive fungal infections are severe and often lead to lethal diseases, and their diagnosis and treatment remains a challenging task. Monoclonal antibodies are highly specific tools that are commonly used to detect microbial pathogens. Their therapeutic application is most advanced in the field of cancer therapy.

Monoclonal antibodies enable fast and sensitive detection of fungal antigens in clinical specimen. A prominent example for this type of application is the detection of galactomannan, a carbohydrate antigen released during Aspergillus fumigatus infection. The therapeutic use of monoclonal antibodies against fungal pathogens has not yet reached clinical practice, however, a plethora of studies published in recent years has demonstrated that certain monoclonal antibodies have the potential to limit or even clear fungal infections.

This Special Issue focuses on studies in which monoclonal antibodies are used to establish new diagnostic applications to combat and eliminate fungal pathogens or to identify interesting antigens that might be useful in either kind of approach.

Prof. Dr. Frank Ebel
Prof. Dr. Carlos Pelleschi Taborda
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Fungi is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • monoclonal antibodies
  • diagnostics
  • therapy
  • antigens

Published Papers (5 papers)

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Research

10 pages, 3035 KiB  
Article
Tocilizumab Induces IL-10-Mediated Immune Tolerance in Invasive Candidiasis
by Zhaohong Tan, Michelle Meng Huang Mok, Win Mar Soe, Thomas Paulraj Thamboo, Jessamine Geraldine Goh, Qi Hui Sam, Motomi Osato, Sharada Ravikumar and Louis Yi Ann Chai
J. Fungi 2021, 7(8), 656; https://doi.org/10.3390/jof7080656 - 13 Aug 2021
Cited by 3 | Viewed by 1999
Abstract
The existence of a hyperinflammatory state has been observed in patients with invasive fungal infections (IFI). It is being postulated whether morbidity from IFI may, in part, be a consequence of an unnecessarily prolonged or exaggerated proinflammatory immune response including interleukin 6 (IL-6) [...] Read more.
The existence of a hyperinflammatory state has been observed in patients with invasive fungal infections (IFI). It is being postulated whether morbidity from IFI may, in part, be a consequence of an unnecessarily prolonged or exaggerated proinflammatory immune response including interleukin 6 (IL-6) post-infection, in a host with dysregulated or compromised immunity. This, in turn, induces collateral host injury at the tissue and organ level, leading to adverse outcomes. Tocilizumab has become widely used as an immunomodulator in the treatment of inflammatory conditions. Here, we evaluated the use of tocilizumab to curb post-infective inflammatory flare in the setting of an in-vivo mouse model for invasive candidiasis. Following Candida infection, the tocilizumab-treated mice showed improved short-term survival compared with the saline-treated control mice. There was a reduced inflammatory response mounted by the host, coupled with reduced IL-6 but increased IL-10 levels. TNF-α and IFN-γ responses were not affected. Tocilizumab facilitated immune tolerance by selectively inducing IL-10, producing CD8α+ conventional dendritic cells (DCs) and peripheral T-regulatory cells, over CD11b+ conventional DCs and plasmacytoid DCs. We demonstrate here the sequelae from immunomodulatory manipulation and the basis whereby the use of monoclonal antibodies may be further explored in IFI. Full article
(This article belongs to the Special Issue Monoclonal Antibodies as Tools to Diagnose and Treat Fungal Infection)
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8 pages, 822 KiB  
Article
Reinvestigation of Carbohydrate Specificity of EBCA-1 Monoclonal Antibody Used for the Detection of Candida Mannan
by Vadim B. Krylov, Arsenii S. Solovev, Ilya A. Puchkin, Dmitry V. Yashunsky, Anna V. Antonets, Olga Y. Kutsevalova and Nikolay E. Nifantiev
J. Fungi 2021, 7(7), 504; https://doi.org/10.3390/jof7070504 - 24 Jun 2021
Cited by 7 | Viewed by 1932
Abstract
Monoclonal antibody EBCA-1 is used in the sandwich immune assay for the detection of circulating Candida mannan in blood sera samples for the diagnosis of invasive candidiasis. To reinvestigate carbohydrate specificity of EBCA-1, a panel of biotinylated oligosaccharides structurally related to distinct fragments [...] Read more.
Monoclonal antibody EBCA-1 is used in the sandwich immune assay for the detection of circulating Candida mannan in blood sera samples for the diagnosis of invasive candidiasis. To reinvestigate carbohydrate specificity of EBCA-1, a panel of biotinylated oligosaccharides structurally related to distinct fragments of Candida mannan were loaded onto a streptavidin-coated plate to form a glycoarray. Its use demonstrated that EBCA-1 recognizes the trisaccharide β-Man-(1→2)-α-Man-(1→2)-α-Man and not homo-α-(1→2)-linked pentamannoside, as was reported previously. Full article
(This article belongs to the Special Issue Monoclonal Antibodies as Tools to Diagnose and Treat Fungal Infection)
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21 pages, 2914 KiB  
Article
Aspergillus fumigatus and Its Allergenic Ribotoxin Asp f I: Old Enemies but New Opportunities for Urine-Based Detection of Invasive Pulmonary Aspergillosis Using Lateral-Flow Technology
by Genna Davies, Oski Singh, Juergen Prattes, Martin Hoenigl, Paul W. Sheppard and Christopher R. Thornton
J. Fungi 2021, 7(1), 19; https://doi.org/10.3390/jof7010019 - 31 Dec 2020
Cited by 3 | Viewed by 3810
Abstract
Invasive pulmonary aspergillosis (IPA) caused by Aspergillus fumigatus is a life-threatening lung disease of immunocompromised patients. Diagnosis currently relies on non-specific chest CT, culture of the fungus from invasive lung biopsy, and detection of the cell wall carbohydrate galactomannan (GM) in serum or [...] Read more.
Invasive pulmonary aspergillosis (IPA) caused by Aspergillus fumigatus is a life-threatening lung disease of immunocompromised patients. Diagnosis currently relies on non-specific chest CT, culture of the fungus from invasive lung biopsy, and detection of the cell wall carbohydrate galactomannan (GM) in serum or in BAL fluids recovered during invasive bronchoscopy. Urine provides an ideal bodily fluid for the non-invasive detection of pathogen biomarkers, with current urine-based immunodiagnostics for IPA focused on GM. Surrogate protein biomarkers might serve to improve disease detection. Here, we report the development of a monoclonal antibody (mAb), PD7, which is specific to A. fumigatus and related species in the section Fumigati, and which binds to its 18 kDa ribotoxin Asp f I. Using PD7, we show that the protein is secreted during hyphal development, and so represents an ideal candidate for detecting invasive growth. We have developed a lateral-flow device (Afu-LFD®) incorporating the mAb which has a limit of detection of ~15 ng Asp f I/mL urine. Preliminary evidence of the test’s diagnostic potential is demonstrated with urine from a patient with acute lymphoid leukaemia with probable IPA. The Afu-LFD® therefore provides a potential novel opportunity for non-invasive urine-based detection of IPA caused by A. fumigatus. Full article
(This article belongs to the Special Issue Monoclonal Antibodies as Tools to Diagnose and Treat Fungal Infection)
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22 pages, 3253 KiB  
Article
Protective Efficacy of Lectin-Fc(IgG) Fusion Proteins In Vitro and in a Pulmonary Aspergillosis In Vivo Model
by Claudia Rodriguez-de la Noval, Susana Ruiz Mendoza, Diego de Souza Gonçalves, Marina da Silva Ferreira, Leandro Honorato, José Mauro Peralta, Leonardo Nimrichter and Allan J. Guimarães
J. Fungi 2020, 6(4), 250; https://doi.org/10.3390/jof6040250 - 27 Oct 2020
Cited by 7 | Viewed by 2618
Abstract
Aspergillosis cases by Aspergillus fumigatus have increased, along with fungal resistance to antifungals, urging the development of new therapies. Passive immunization targeting common fungal antigens, such as chitin and β-glucans, are promising and would eliminate the need of species-level diagnosis, thereby expediting the [...] Read more.
Aspergillosis cases by Aspergillus fumigatus have increased, along with fungal resistance to antifungals, urging the development of new therapies. Passive immunization targeting common fungal antigens, such as chitin and β-glucans, are promising and would eliminate the need of species-level diagnosis, thereby expediting the therapeutic intervention. However, these polysaccharides are poorly immunogenic. To overcome this drawback, we developed the lectin-Fc(IgG) fusion proteins, Dectin1-Fc(IgG2a), Dectin1-Fc(IgG2b) and wheat germ agglutinin (WGA)-Fc(IgG2a), based on their affinity to β-1,3-glucan and chitooligomers, respectively. The WGA-Fc(IgG2a) previously demonstrated antifungal activity against Histoplasma capsulatum, Cryptococcus neoformans and Candida albicans. In the present work, we evaluated the antifungal properties of these lectin-Fc(s) against A. fumigatus. Lectin-Fc(IgG)(s) bound in a dose-dependent manner to germinating conidia and this binding increased upon conidia germination. Both lectin-Fc(IgG)(s) displayed in vitro antifungal effects, such as inhibition of conidia germination, a reduced length of germ tubes and a diminished biofilm formation. Lectin-Fc(IgG)(s) also enhanced complement deposition on conidia and macrophage effector functions, such as increased phagocytosis and killing of fungi. Finally, administration of the Dectin-1-Fc(IgG2b) and WGA-Fc(IgG2a) protected mice infected with A. fumigatus, with a 20% survival and a doubled life-span of the infected mice, which was correlated to a fungal burden reduction in lungs and brains of treated animals. These results confirm the potential of lectin-Fc(IgGs)(s) as a broad-spectrum antifungal therapeutic. Full article
(This article belongs to the Special Issue Monoclonal Antibodies as Tools to Diagnose and Treat Fungal Infection)
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11 pages, 2775 KiB  
Article
Paracoccidioides HSP90 Can Be Found in the Cell Surface and Is a Target for Antibodies with Therapeutic Potential
by Ágata Nogueira D’Áurea Moura, Diane Sthefany Lima de Oliveira, Verenice Paredes, Letícia Barboza Rocha, Fabiana Freire Mende de Oliveira, Gustavo Meirelles Lessa, Juan Fernando Riasco-Palacios, Arturo Casadevall, Patrícia Albuquerque, Maria Sueli Soares Felipe, Roxane Maria Fontes Piazza and André Moraes Nicola
J. Fungi 2020, 6(4), 193; https://doi.org/10.3390/jof6040193 - 28 Sep 2020
Cited by 4 | Viewed by 2871
Abstract
Paracoccidioidomycosis (PCM) is one of the most frequent systemic mycoses in Latin America. It affects mainly male rural workers in impoverished regions, and the therapy can last up to two years or use drugs that are very toxic. Given the need for novel [...] Read more.
Paracoccidioidomycosis (PCM) is one of the most frequent systemic mycoses in Latin America. It affects mainly male rural workers in impoverished regions, and the therapy can last up to two years or use drugs that are very toxic. Given the need for novel safe and effective approaches to treat PCM, we have been developing monoclonal antibodies (mAbs) that could be used not only to block specific fungal targets, but also modulate the host’s antifungal immunity. In this work we show the generation of and promising results with an mAb against Heat Shock Protein (HSP)90, a molecular chaperone that is an important virulence factor in fungi. Using recombinant Paracoccidioides lutzii (Pb01) and P. brasiliensis (Pb18) HSP90 proteins produced in E. coli, we immunized mice and generated polyclonal antibodies and an IgG1 hybridoma mAb. The proteins were very immunogenic and both the polyclonal serum and mAb were used in immunofluorescence experiments, which showed binding of antibodies to the yeast cell surface. The mAb successfully opsonized P. lutzii and P. brasiliensis cells in co-incubations with J774.16 macrophage-like cells. Our results suggest that this mAb could serve as the basis for new immunotherapy regimens for PCM. Full article
(This article belongs to the Special Issue Monoclonal Antibodies as Tools to Diagnose and Treat Fungal Infection)
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