Article
Microbiology
Hamideh Raeisi, Masoumeh Azimirad, Hamid Asadzadeh Aghdaei, Amir-Hassan Zarnani, Jalal Abdolalizadeh, Abbas Yadegar, Mohammad Reza Zali
Summary: In this study, phage display was used to select single-chain variable fragments (scFvs) that specifically target the major virulence factors, TcdA and TcdB, of Clostridioides difficile. The selected scFvs showed high neutralizing activity and could decrease the mRNA expression of inflammatory markers in treated cells. Molecular docking revealed that the interaction between scFvs and toxins was mainly restricted to the CROP domain. These findings provide insights for the development of neutralizing scFvs against C. difficile toxins using phage display.
MICROBIOLOGY SPECTRUM
(2023)
Article
Agriculture, Multidisciplinary
Jin-xing Song, Meng-xiang Wang, Yi-xuan Zhang, Bo Wan, Yong-kun Du, Guo-qing Zhuang, Zi-bin Li, Song-lin Qiao, Rui Geng, Ya-nan Wu, Gai-ping Zhang
Summary: This study generated an ASFV antibody phage-display library, screened a specific single-chain antibody against ASFV major capsid protein, and identified a conserved epitope peptide that can promote the maturation of immune cells and be effectively uptaken by dendritic cells.
JOURNAL OF INTEGRATIVE AGRICULTURE
(2023)
Article
Biotechnology & Applied Microbiology
Yaqi Yang, Siji Nian, Lin Li, Xue Wen, Qin Liu, Bo Zhang, Yu Lan, Qing Yuan, Yingchun Ye
Summary: Enhanced EphA2 expression is a crucial target for anti-tumor therapy, with high affinity scFvs against EphA2 successfully screened from an immune library constructed using PBMCs from cancer patients. Modified antibodies showed improved affinity and the ability to bind to EphA2, tumor cells, and tissues, inhibiting tumor growth to some extent. This study highlights the potential of immune libraries from cancer patients in screening for high-affinity antibodies with therapeutic effects.
Article
Pharmacology & Pharmacy
Sebastian Heber, Lara Barthold, Jan Baier, Panagiotis Papatheodorou, Giorgio Fois, Manfred Frick, Holger Barth, Stephan Fischer
Summary: C. difficile produces toxins TcdA and TcdB, which cause CDAD by targeting small GTPases and disrupting intestinal epithelial barrier. Conventional antibiotics do not target these toxins, therefore directly targeting the exotoxins provides a promising treatment approach. Recent findings show that ambroxol reduces toxin-induced cytotoxicity and glucosylation, and could be considered as a therapeutic option for CDAD.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Florian Stieglitz, Ralf Gerhard, Rabea Hoenig, Klaudia Giehl, Andreas Pich
Summary: A Clostridioides difficile infection (CDI) is a common hospital-acquired infection worldwide. The virulence factors TcdA and TcdB inhibit small Rho-GTPases, leading to cytopathic effects, colon epithelium barrier dysfunction, and inflammation. A large-scale phosphoproteomic study revealed the central role of RAS in the glucosyltransferase-independent effect of TcdB, and identified apolipoprotein C-III (APOC3) as a potential crucial factor in CDI-induced inflammation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Immunology
Anne di Tommaso, Matthieu O. Juste, Zineb Lakhrif, Marie-Noelle Mevelec, Coraline Borowczyk, Pierre Hammeni, Guillaume Desoubeaux, Nathalie Van Langendonck, Francoise Debierre-Grockiego, Nicolas Aubrey, Isabelle Dimier-Poisson
Summary: Research shows that antibody fragments targeting the major surface protein SAG1 have the potential to inhibit the proliferation of Toxoplasma gondii, providing a promising avenue for specific treatment against congenital toxoplasmosis in the future.
JOURNAL OF INFECTIOUS DISEASES
(2021)
Article
Biochemical Research Methods
Eeva-Christine Brockmann, Mikko Pyykko, Heidi Hannula, Kamran Khan, Urpo Lamminmaki, Tuomas Huovinen
Summary: This study discusses the impact of loop length variation on the structural diversity of antibody libraries. Introducing loop length variation in specific antibody fragments can enhance affinity, especially in CDR-L1 and CDR-H2 loops. The results lay the foundation for developing novel synthetic antibody libraries with unique loop length combinations.
Article
Immunology
Baohua Chen, Kay Perry, Rongsheng Jin
Summary: This study reports the identification of two critical epitopes on the virulence factor TcdA and sheds new insights into the neutralizing mechanisms of two potent camelid antibodies against TcdA. These findings provide potential targets for the development of epitope-focused vaccines against TcdA.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Microbiology
Joshua Heuler, Louis-Charles Fortier, Xingmin Sun
Summary: Clostridioides difficile, formerly known as Clostridium difficile, is the causative agent of C. difficile infections, which pose challenges in healthcare settings. Antibiotic-induced dysbiosis allows C. difficile colonization in the gut. Phage infection offers potential new treatment strategies against C. difficile infections.
FEMS MICROBIOLOGY REVIEWS
(2021)
Review
Microbiology
Joshua Heuler, Louis-Charles Fortier, Xingmin Sun
Summary: Clostridioides difficile, previously known as Clostridium difficile, is the causative agent of CDI. Antibiotics-induced dysbiosis of the microbiota is the primary factor allowing C. difficile to colonize the gut and cause diseases. Phages infecting C. difficile could offer new treatment strategies and insights into its biology.
FEMS MICROBIOLOGY REVIEWS
(2021)
Article
Biotechnology & Applied Microbiology
Ying Sun, Yongrong Zhang, Hua Yu, Ashley Saint Fleur, Di Yu, Zhiyong Yang, Hanping Feng
Summary: In this proof-of-concept study, a versatile platform was developed using Saccharomyces cerevisiae to rapidly identify antibodies with both high affinity and neutralizing activity. The platform successfully expressed engineered chimeric-bispecific Fab antibodies and enabled the construction and enrichment of a combinatorial Fab library. The screening process led to the identification of two unique neutralizers that can neutralize the cytotoxicity of TcdB.
MICROBIAL CELL FACTORIES
(2023)
Article
Immunology
Kai-Thomas Schneider, Toni Kirmann, Esther Veronika Wenzel, Jan-Hendrik Grosch, Saskia Polten, Doris Meier, Marlies Becker, Paul Matejtschuk, Michael Hust, Giulio Russo, Stefan Duebel
Summary: Generation of sequence defined antibodies from universal libraries by phage display has been established as a robust method. ScFv-Fcs can be effective as neutralizing antibodies against a panel of pathogens and toxins, but may have variable stability. A generic lyophilization protocol has been developed to improve their shelf life, showing preservation of initial properties without compromising binding activity after storage.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Lara Barthold, Sebastian Heber, Christoph Q. Schmidt, Marion Gradl, Gilbert Weidinger, Holger Barth, Stephan Fischer
Summary: Rising incidences and mortalities of Clostridioides difficile infections (CDIs) have raised concerns. In this study, the protective effect of human antimicrobial peptide alpha-defensin-6 against CDI toxins TcdA and TcdB was demonstrated. The peptide prevented toxin-mediated glucosylation of Rho-GTPases, protecting cells, epithelial barriers, and zebrafish embryos from toxic effects. It was found that alpha-defensin-6 rapidly sequesters the toxin into complexes, preventing its cytotoxic activity. These findings contribute to the understanding of how human peptides neutralize bacterial protein toxins and may guide the development of novel therapeutic options against CDIs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Microbiology
Hamideh Raeisi, Masoumeh Azimirad, Hamid Asadzadeh Aghdaei, Abbas Yadegar, Mohammad Reza Zali
Summary: Clostridioides difficile (C. difficile) is a common cause of nosocomial diarrhea and the emergence of hypervirulent strains has led to efforts in developing accurate diagnostic methods. Antibody-based ultrasensitive diagnostic platforms, particularly those using recombinant antibodies (rAbs), have shown promising results in both research and clinical settings. These platforms offer high sensitivity and specificity, and the use of rAb technologies allows for faster and more cost-effective antibody production.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Pierre-Emmanuel Baurand, Jeremy Balland, Chloe Reynas, Melanie Ramseyer, Delphine Vivier, Pierre-Simon Bellaye, Bertrand Collin, Catherine Paul, Franck Denat, Kamal Asgarov, Jean-Rene Pallandre, Laurence Ringenbach
Summary: The study developed an ScFv mouse phage-display library to obtain small fragment antibodies against human LRRC15 for molecular imaging purposes, demonstrating the relevance for the fast-track development of small antibodies for imaging and/or immunotherapy purposes. The library had a high insertion rate and enrichment through screening, leading to the identification of specific candidates for further development.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Multidisciplinary
Sebastian Ronneberger, Junfang Zhang, Yuxin Liu, Felix F. F. Loeffler
Summary: This study demonstrates a printing method based on laser-driven deposition of solid polymer ink, which allows for printing on various substrates without pretreatment. The method has a printing precision of <1 μm and introduces the concept of sub-positions with overlapping spots, enabling high-resolution fluorescent labels and rapid machine learning-supported readout based on low-resolution fluorescence imaging.
ADVANCED FUNCTIONAL MATERIALS
(2023)
Article
Chemistry, Multidisciplinary
Yuxin Liu, Xingjun Zhu, Zheng Wei, Kefan Wu, Junfang Zhang, Francesco G. Mutti, Hong Zhang, Felix F. Loeffler, Jing Zhou
Summary: A multi-channel lanthanide nanocomposite was used to achieve tailored synergistic treatment of multiple subcutaneous orthotopic tumors under non-uniform whole-body infrared irradiation prescription. The nanocomposite reduces intratumoral glutathione by simultaneously activating the fluorescence and photothermal channels, enabling customized prescriptions to be made based on individual information provided by fluorescence. With an accessional therapeutic laser system, customized synergistic treatment of subcutaneous orthotopic cancer cases with multiple tumors is possible with both high efficacy and minimized side effects.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Clinical Neurology
Stephan Steinke, Toni Kirmann, Eleonora A. Loi, Jana Nerlich, Iron Weichard, Philipp Kuhn, Torsten Bullmann, Andreas Ritzau-Jost, Filiz Sila Rizalar, Harald Pruess, Volker Haucke, Christian Geis, Michael Hust, Stefan Hallermann
Summary: Researchers developed and validated a construct that can neutralize autoantibodies from patients with NMDAR encephalitis, preventing receptor internalization and memory deficits in a mouse model. This approach offers a promising strategy for fast and specific treatment of NMDAR encephalitis.
Article
Nanoscience & Nanotechnology
Junfang Zhang, Yuxin Liu, Christian Njel, Sebastian Ronneberger, Nadezda V. V. Tarakina, Felix F. F. Loeffler
Summary: Counterfeiting not only causes trillion-dollar economic losses annually, but also threatens human health, social equity, and national security. Researchers have developed a nanoprinting-assisted flash synthesis approach to create fluorescent nanofilms with physical unclonable function micropatterns in milliseconds. These unclonable patterns can be quickly and independently read out by fluorescence and topography scanning, greatly enhancing their security.
NATURE NANOTECHNOLOGY
(2023)
Article
Multidisciplinary Sciences
Nora Langreder, Dorina Schaeckermann, Doris Meier, Marlies Becker, Maren Schubert, Stefan Duebel, Thomas Reinard, Stefanie Figge-Wegener, Kristine Rossbach, Wolfgang Baeumer, Simone Ladel, Michael Hust
Summary: Insect bite hypersensitivity (IBH), the most common allergic skin disease in horses, is caused by bites from Culicoides spp. insects, resulting in a type I/IVb allergy involving eosinophil cells. A potential treatment option is the use of a therapeutic antibody targeting equine interleukin 5, the main activator and regulator of eosinophils. Through phage display and in vitro affinity maturation, an antibody named NOL226-2-D10 was developed, showing strong inhibition of interleukin 5 binding and satisfactory producibility. This antibody is a promising candidate for in vivo studies to treat equine IBH.
SCIENTIFIC REPORTS
(2023)
Article
Cell Biology
Tom Pieper, Kristian Daniel Ralph Roth, Viktor Glaser, Tobias Riet, Laura Elisa Buitrago-Molina, Maike Hagedorn, Maren Lieber, Michael Hust, Fatih Noyan, Elmar Jaeckel, Matthias Hardtke-Wolenski
Summary: Adoptive transfer of antigen-specific regulatory T cells (Tregs) has shown promising results in treating autoimmune diseases. However, obtaining sufficient antigen-specific Tregs from patients with autoimmune disorders remains challenging. In this study, researchers aimed to generate CARs against TSPAN7, a membrane protein highly expressed on the surface of pancreatic beta cells, using phage display technology. Although the resulting CARs were functional and specifically activated by the target structure, they could not recognize TSPAN7 on the surface of beta cells. This study demonstrates the power of CAR technology in generating antigen-specific T cells and provides new approaches for functional CAR generation.
Letter
Health Care Sciences & Services
Fanglei Zuo, Rui Sun, Hassan Abolhassani, Likun Du, Yating Wang, Stelios Vlachiotis, Federico Bertoglio, Maren Schubert, Nima Rezaei, Zahra Chavoshzadeh, Concetta Guerra, Andrea Cavalli, Juni Andrell, Makiko Kumagai-Braesch, Yintong Xue, Yunlong Cao, Michael Hust, Davide F. Robbiani, Xiaoliang Sunney Xie, Lennart Hammarstrom, Harold Marcotte, Qiang Pan-Hammarstrom
LANCET REGIONAL HEALTH-WESTERN PACIFIC
(2023)
Article
Chemistry, Multidisciplinary
Yuxin Liu, Zheng Wei, Matteo Damian, Xingjun Zhu, Tanja Knaus, Hong Zhang, Francesco G. Mutti, Felix F. Loeffler
Summary: Recyclable fluorescent probes with enhanced thermo-/chemo-stability have been proposed, which can maintain outstanding serodiagnostic performance after multiple recycling and storage at elevated temperatures. These probes can be designed to detect various biomarkers of clinical importance using different enzymes.
ADVANCED MATERIALS
(2023)
Article
Multidisciplinary Sciences
Junfang Zhang, Yuntao Zhu, Christian Njel, Yuxin Liu, Pietro Dallabernardina, Molly M. Stevens, Peter H. Seeberger, Oleksandr Savateev, Felix F. Loeffler
Summary: In this study, a new synthesis strategy for carbon nitride photoelectrodes was introduced through advanced film generation techniques. This method involved spin coating pretreatment of a conductive substrate with a multipurpose polymer and a supramolecular precursor, followed by chemical vapor deposition to synthesize dual-layer carbon nitride photoelectrodes. The polymer improved the polymerization degree and electrical conductivity of carbon nitride, leading to state-of-the-art photoelectrochemical performance and high yields in C-H functionalization.
NATURE COMMUNICATIONS
(2023)
Article
Immunology
Sebastian Lutz, Katja Klausz, Anca-Maria Albici, Lea Ebinger, Lea Sellmer, Hannah Teipel, Andre Frenzel, Anna Langner, Dorothee Winterberg, Steffen Krohn, Michael Hust, Thomas Schirrmann, Stefan Duebel, Regina Scherliess, Andreas Humpe, Martin Gramatzki, Christian Kellner, Matthias Peipp
Summary: This study successfully activated natural killer cells and induced lysis of lymphoma cells by preparing novel bispecific antibodies. The study also found that co-administration with specific monoclonal antibodies or bispecific T cell engagers enhanced antibody-dependent cell-mediated cytotoxicity and T cell activation. Furthermore, the study proposed a combinatorial approach targeting multiple tumor antigens, which has the potential to optimize antibody cancer therapies.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Anna Christina Dragon, Luca Marie Beermann, Melina Umland, Agnes Bonifacius, Chiara Malinconico, Louisa Ruhl, Patrik Kehler, Johanna Gellert, Lisa Weiss, Sarah Mayer-Hain, Katharina Zimmermann, Sebastian Riese, Felicitas Thol, Gernot Beutel, Britta Maecker-Kolhoff, Fumiichiro Yamamoto, Rainer Blasczyk, Axel Schambach, Michael Hust, Michael Hudecek, Britta Eiz-Vesper
Summary: CD176-CAR-T cells specifically recognize the widely expressed CD176 antigen on cancer cells, providing a promising approach for the treatment of various blood and solid tumors while avoiding on-target/off-tumor cytotoxicity.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Federico Bertoglio, Ya-Ping Ko, Sheila Thomas, Liliana Giordano, Francesca Romana Scommegna, Doris Meier, Saskia Polten, Marlies Becker, Srishtee Arora, Michael Hust, Magnus Hook, Livia Visai
Summary: Staphylococcus aureus pathogenesis is mediated by a variety of virulence factors, including coagulase (Coa) and extracellular fibrinogen-binding protein (Efb) which interact with fibrinogen (Fg). This study describes the selection and characterization of fully human monoclonal antibodies against the C-terminal of Coa, which can also recognize and block the interaction between Coa/Efb and Fg. The discovery of these antibodies provides a novel therapeutic option against S. aureus.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biology
Gertrudis Rojas, Ernesto Relova-Hernandez, Annia Perez-Riveron, Camila Castro-Martinez, Osmany Diaz-Bravo, Yanelys Cabrera Infante, Tania Gomez, Joaquin Solozabal, Ana Beatriz DiazBravo, Maren Schubert, Marlies Becker, Beatriz Perez-Masson, Dayana Perez-Martinez, Rydell Alvarez-Arzola, Osmany Guirola, Glay Chinea, Luis Graca, Stefan Dubel, Kalet Leon, Tania Carmenate
Summary: Engineered interleukin-2 (IL-2) variants with improved electrostatic complementarity to the IL-2 receptor beta chain and faster association kinetics enhance immune effector responses and anti-tumor effects in vivo. These variants have an accumulation of negatively charged residues at the interface, providing better electrostatic complementarity and faster association kinetics. These findings differentiate them from previously reported superkines.
COMMUNICATIONS BIOLOGY
(2023)
Article
Engineering, Electrical & Electronic
Marco Hepp, Huize Wang, Katharina Derr, Simon Delacroix, Sebastian Ronneberger, Felix F. Loeffler, Benjamin Butz, Volker Strauss
Summary: This study describes the mechanical properties of turbostratically graphitized carbon films obtained by carbon laser-patterning, and explores their potential application as bending or mechanical pressure sensors.
NPJ FLEXIBLE ELECTRONICS
(2022)