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33 results on '"Lindemann, Claudia"'

3. Preclinical efficacy and pharmacokinetics of an RNA-encoded T cell–engaging bispecific antibody targeting human claudin 6

Author

Stadler, Christiane R., primary, Ellinghaus, Ursula, additional, Fischer, Leyla, additional, Bähr-Mahmud, Hayat, additional, Rao, Martin, additional, Lindemann, Claudia, additional, Chaturvedi, Anuhar, additional, Scharf, Caroline, additional, Biermann, Imke, additional, Hebich, Bernhard, additional, Malz, Alexandra, additional, Beresin, Georg, additional, Falck, Georg, additional, Häcker, Aline, additional, Houben, Astrid, additional, Erdeljan, Michael, additional, Wolf, Kristina, additional, Kullmann, Maximilian, additional, Chang, Philip, additional, Türeci, Özlem, additional, and Şahin, Uğur, additional

Published
2024
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4. A multivalent mRNA monkeypox virus vaccine (BNT166) protects mice and macaques from orthopoxvirus disease

Author

Zuiani, Adam, primary, Dulberger, Charles L., additional, De Silva, Nilushi S., additional, Marquette, Meghan, additional, Lu, Yu-Jung, additional, Palowitch, Gavin M., additional, Dokic, Anja, additional, Sanchez-Velazquez, Ricardo, additional, Schlatterer, Katja, additional, Sarkar, Sanjay, additional, Kar, Swagata, additional, Chawla, Bhavna, additional, Galeev, Alibek, additional, Lindemann, Claudia, additional, Rothenberg, Daniel A., additional, Diao, Huitian, additional, Walls, Alexandra C., additional, Addona, Theresa A., additional, Mensa, Federico, additional, Vogel, Annette B., additional, Stuart, Lynda M., additional, van der Most, Robbert, additional, Srouji, John R., additional, Türeci, Özlem, additional, Gaynor, Richard B., additional, Şahin, Uğur, additional, and Poran, Asaf, additional

Published
2024
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6. Understanding early transcriptional events in Staphylococcus aureus infection

Author

Lindemann, Claudia, Wyllie, David, and Wilson, Daniel

Subjects
616.9, Next Generation Sequencing, Vaccines, Bacteria, Communicable diseases, Staphylococcus aureus, rsp gene, Antigen Identification, In vivo RNA transcription, Vaccine Development
Abstract

Staphylococcus aureus remains an important pathogen, which, due to its capability to develop antimicrobial resistance, imposes an increasing threat to human health. Developing preventive means to decrease disease burden is a major aim. However, the development of an S. aureus vaccine, which would be one strategy to achieve such goals, has been complicated through limited understanding of the bacterium's pathogenic mechanisms. This work uses four approaches to address these limitations: Firstly, a reproducible RNA sequencing based method for the determination of gene transcription by S. aureus in vivo during mammalian infection. Secondly, examination of the impact of the bacterial transcription regulator 'Rsp' on the bacterium, which shows that mutations in this gene have profound functional and transcriptional impacts. Thirdly, by examining the in vivo transcription of multiple S. aureus strains during infection, proposing a 'core in vivo transcriptome' of induced genes under the conditions tested. Some of these genes are known to be involved in pathogenesis, others are not completely characterised and may represent suitable vaccine antigens. Finally, this work addresses limited understanding of S. aureus pathogenesis through defining transcriptional changes in vivo, which are induced by an altered immune response in immunised hosts. Together, this body of work contributes to the understanding of S. aureus pathogenesis and provides candidate antigens for future vaccine development.

Published
2017

7. Preclinical characterization of an mRNA-encoded anti-Claudin 18.2 antibody

Author

Bähr-Mahmud, Hayat, primary, Ellinghaus, Ursula, additional, Stadler, Christiane R., additional, Fischer, Leyla, additional, Lindemann, Claudia, additional, Chaturvedi, Anuhar, additional, Diekmann, Jan, additional, Wöll, Stefan, additional, Biermann, Imke, additional, Hebich, Bernhard, additional, Scharf, Caroline, additional, Siefke, Manuela, additional, Roth, Alexandra S., additional, Rao, Martin, additional, Brettschneider, Kerstin, additional, Ewen, Eva-Maria, additional, Şahin, Uğur, additional, and Türeci, Özlem, additional

Published
2023
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9. Toxicological Assessments of a Pandemic COVID-19 Vaccine—Demonstrating the Suitability of a Platform Approach for mRNA Vaccines

Author

Rohde, Cynthia M., primary, Lindemann, Claudia, additional, Giovanelli, Michael, additional, Sellers, Rani S., additional, Diekmann, Jan, additional, Choudhary, Shambhunath, additional, Ramaiah, Lila, additional, Vogel, Annette B., additional, Chervona, Yana, additional, Muik, Alexander, additional, and Sahin, Ugur, additional

Published
2023
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10. Natural mutations in a Staphylococcus aureus virulence regulator attenuate cytotoxicity but permit bacteremia and abscess formation

Author

Das, Sudip, Lindemann, Claudia, Young, Bernadette C., Muller, Julius, Österreich, Babett, Ternette, Nicola, Winkler, Ann-Cathrin, Paprotka, Kerstin, Reinhardt, Richard, Förstner, Konrad U., Allen, Elizabeth, Flaxman, Amy, Yamaguchi, Yuko, Rollier, Christine S., van Diemen, Pauline, Blättner, Sebastian, Remmele, Christian W., Selle, Martina, Dittrich, Marcus, Müller, Tobias, Vogel, Jörg, Ohlsen, Knut, Crook, Derrick W., Massey, Ruth, Wilson, Daniel J., Rudel, Thomas, Wyllie, David H., and Fraunholz, Martin J.

Published
2016

20. MRI Based Localisation and Quantification of Abscesses following Experimental S. aureus Intravenous Challenge: Application to Vaccine Evaluation

Author

Allen, Elizabeth R., van Diemen, Pauline, Yamaguchi, Yuko, Lindemann, Claudia, Soilleux, Elizabeth, Rollier, Christine, Hill, Fergal, Schneider, Jurgen, Wyllie, David H., Wyllie, David H [0000-0002-9155-6228], and Apollo - University of Cambridge Repository

Subjects
Bacterial Diseases, Staphylococcus, lcsh:Medicine, Pathology and Laboratory Medicine, Kidney, Diagnostic Radiology, Mice, Medicine and Health Sciences, Public and Occupational Health, Enzyme-Linked Immunoassays, lcsh:Science, Vaccines, Mice, Inbred BALB C, Radiology and Imaging, Staphylococcal Vaccines, Staphylococcal Infections, Magnetic Resonance Imaging, Vaccination and Immunization, Abscess, Bacterial Pathogens, Infectious Diseases, Medical Microbiology, Administration, Intravenous, Female, Kidney Diseases, Anatomy, Pathogens, Research Article, Staphylococcus aureus, Histology, Imaging Techniques, Immunology, Research and Analysis Methods, Microbiology, Signs and Symptoms, Diagnostic Medicine, Animals, Immunoassays, Microbial Pathogens, Staphylococcal Infection, Bacteria, lcsh:R, Organisms, Biology and Life Sciences, Kidneys, Renal System, Abscesses, Immunologic Techniques, lcsh:Q, Preventive Medicine
Abstract

PURPOSE: To develop and validate a sensitive and specific method of abscess enumeration and quantification in a preclinical model of Staphylococcus aureus infection. METHODS: S. aureus infected murine kidneys were fixed in paraformaldehyde, impregnated with gadolinium, and embedded in agar blocks, which were subjected to 3D magnetic resonance microscopy on a 9.4T MRI scanner. Image analysis techniques were developed, which could identify and quantify abscesses. The result of this imaging was compared with histological examination. The impact of a S. aureus Sortase A vaccination regime was assessed using the technique. RESULTS: Up to 32 murine kidneys could be imaged in a single MRI run, yielding images with voxels of about 25 μm3. S. aureus abscesses could be readily identified in blinded analyses of the kidneys after 3 days of infection, with low inter-observer variability. Comparison with histological sections shows a striking correlation between the two techniques: all presumptive abscesses identified by MRI were confirmed histologically, and histology identified no abscesses not evident on MRI. In view of this, simulations were performed assuming that both MRI reconstruction, and histology examining all sections of the tissue, were fully sensitive and specific at abscess detection. This simulation showed that MRI provided more sensitive and precise estimates of abscess numbers and volume than histology, unless at least 5 histological sections are taken through the long axis of the kidney. We used the MRI technique described to investigate the impact of a S. aureus Sortase A vaccine. CONCLUSION: Post mortem MRI scanning of large batches of fixed organs has application in the preclinical assessment of S. aureus vaccines.

Published
2016

26. A phase I/II dose escalation and expansion trial to evaluate safety and preliminary efficacy of BNT141 in patients with claudin-18.2-positive solid tumors.

Author

Papadopoulos, Kyriakos P., Tehfe, Mustapha, Abdul Razak, Albiruni Ryan, Pant, Shubham, Chung, Vincent, Rasco, Drew W., Jamal, Rahima, Willis, Jason, Fuentes Antrás, Jesús, Brettschneider, Kerstin, Zamorski, Alexandra, Bähr-Mahmud, Hayat, Koseoglu, Secil, Chang, Philip K, Lindemann, Claudia, Schlitter, Anna Melissa, Magenheim, Rita, De Mattos-Arruda, Leticia, Türeci, Özlem, and Sahin, Ugur

Published
2023
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27. A phase I/II dose escalation trial with expansion cohorts to evaluate safety and preliminary efficacy of BNT142 in patients with prospectively confirmed claudin 6-positive solid tumors.

Author

Yap, Timothy A., Papadopoulos, Kyriakos P., Garralda, Elena, Spira, Alexander I., Calvo, Emiliano, Saavedra, Omar, Ramon-Patino, Jorge L, Stadler, Christiane, Koseoglu, Secil, Chang, Philip K, Ellinghaus, Ursula, Lindemann, Claudia, Ewen, Eva-Maria, Zyto, Elzbieta, Zamorski, Alexandra, Martinez, Jorge Luis, De Mattos-Arruda, Leticia, Celik, Ilhan, Türeci, Özlem, and Sahin, Ugur

Published
2023
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31. MRI Based Localisation and Quantification of Abscesses following Experimental S. aureus Intravenous Challenge: Application to Vaccine Evaluation

Author

Allen, Elizabeth R, Van Diemen, Pauline, Yamaguchi, Yuko, Lindemann, Claudia, Soilleux, Elizabeth, Rollier, Christine, Hill, Fergal, Schneider, Jurgen, and Wyllie, David H

Subjects
Mice, Mice, Inbred BALB C, Staphylococcus aureus, Animals, Administration, Intravenous, Female, Kidney Diseases, Staphylococcal Vaccines, Staphylococcal Infections, Kidney, Magnetic Resonance Imaging, Abscess, 3. Good health
Abstract

PURPOSE: To develop and validate a sensitive and specific method of abscess enumeration and quantification in a preclinical model of Staphylococcus aureus infection. METHODS: S. aureus infected murine kidneys were fixed in paraformaldehyde, impregnated with gadolinium, and embedded in agar blocks, which were subjected to 3D magnetic resonance microscopy on a 9.4T MRI scanner. Image analysis techniques were developed, which could identify and quantify abscesses. The result of this imaging was compared with histological examination. The impact of a S. aureus Sortase A vaccination regime was assessed using the technique. RESULTS: Up to 32 murine kidneys could be imaged in a single MRI run, yielding images with voxels of about 25 μm3. S. aureus abscesses could be readily identified in blinded analyses of the kidneys after 3 days of infection, with low inter-observer variability. Comparison with histological sections shows a striking correlation between the two techniques: all presumptive abscesses identified by MRI were confirmed histologically, and histology identified no abscesses not evident on MRI. In view of this, simulations were performed assuming that both MRI reconstruction, and histology examining all sections of the tissue, were fully sensitive and specific at abscess detection. This simulation showed that MRI provided more sensitive and precise estimates of abscess numbers and volume than histology, unless at least 5 histological sections are taken through the long axis of the kidney. We used the MRI technique described to investigate the impact of a S. aureus Sortase A vaccine. CONCLUSION: Post mortem MRI scanning of large batches of fixed organs has application in the preclinical assessment of S. aureus vaccines.

32. Next-Generation Trapping of Protease Substrates by Label-Free Proteomics.

Author

Lindemann C, Thomanek N, Kuhlmann K, Meyer HE, Marcus K, and Narberhaus F

Subjects
ATP-Dependent Proteases, Chromatography, High Pressure Liquid, Data Science, Escherichia coli metabolism, Mass Spectrometry, Peptides chemistry, Proteolysis, Substrate Specificity, Enzyme Assays methods, Peptide Hydrolases metabolism, Proteome, Proteomics methods
Abstract

AAA + proteases (ATPases associated with various cellular activities) shape the cellular protein pool in response to environmental conditions. A prerequisite for understanding the underlying recognition and degradation principles is the identification of as many protease substrates as possible. Most previous studies made use of inactive protease variants to trap substrates, which were identified by 2D-gel based proteomics. Since this method is known for limitations in the identification of low-abundant proteins or proteins with many transmembrane domains, we established a trapping approach that overcomes these limitations. We used a proteolytically inactive FtsH variant (FtsH trap ) of Escherichia coli (E. coli) that is still able to bind and translocate substrates into the proteolytic chamber but no longer able to degrade proteins. Proteins associated with FtsH trap or FtsH wt (proteolytically active FtsH) were purified, concentrated by an 1D-short gel, and identified by LC-coupled mass spectrometry (LC-MS) followed by label-free quantification. The identification of four known FtsH substrates validated this approach and suggests that it is generally applicable to AAA + proteases.

Published
2018
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33. Quantitative redox proteomics: the NOxICAT method.

Author

Lindemann C and Leichert LI

Subjects
Chromatography, Affinity, Chromatography, Ion Exchange, Culture Techniques, Cysteine chemistry, Cysteine metabolism, Escherichia coli physiology, Escherichia coli Proteins chemistry, Escherichia coli Proteins isolation & purification, Isotope Labeling, Mass Spectrometry, Oxidation-Reduction, Oxidative Stress, Proteolysis, Proteomics, Reactive Nitrogen Species metabolism, Reactive Oxygen Species metabolism, Trypsin chemistry, Escherichia coli metabolism, Escherichia coli Proteins metabolism
Abstract

Because of its versatile chemical properties, the amino acid cysteine plays a variety of vital roles in proteins. It can form structure-stabilizing elements (e.g., disulfide bonds), coordinate metal cofactors and is part of the catalytic center of many enzymes. Recently, a new role has been discovered for cysteine: so-called redox-sensitive proteins use the thiol group of cysteine as a specific sensor for Reactive Oxygen Species (ROS) and Reactive Nitrogen Species (RNS). The oxidation of such a redox-active cysteine, e.g., under conditions of elevated cellular ROS or RNS levels (oxidative or nitrosative stress), often results in a reversible thiol modification. This, in turn, might lead to structural changes and altered protein activity. When the oxidative stress subsides, cellular antioxidant systems, including thioredoxin and glutathione can reduce the redox-active cysteine and restore the original structure and activity of the redox-sensitive protein. This makes oxidative thiol modifications an attractive mechanism for cellular redox sensing and signaling.To study the target cysteines of oxidative and nitrosative stress and to quantify the extent of the thiol modifications generated under these conditions, we have recently developed a thiol trapping technique using isotope coded affinity tag (ICAT) chemistry (1). With this method, reduced cysteines are selectively labeled with the isotopically light form of ICAT and oxidized cysteines with the isotopically heavy form of ICAT. Thus we could globally quantify the ratio of reduced and oxidized cysteines in cellular proteins based on the modified peptide masses. Here, we present an expansion of this method, which we term NOxICAT, because it uses ICAT chemistry to detect changes in thiol modifications of proteins upon Nitrosative and Oxidative stress. The NOxICAT-method is a highly specific and quantitative method to study the global changes in the thiol redox state of cellular proteins under a variety of physiological and pathological stress conditions.

Published
2012
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