Immunology and infection research

Development and testing of anti-infective drugs against bacteria and viruses

© Fraunhofer ITEM, Ralf Mohr
The development, formulation and mode of delivery of anti-infective agents are key research topics at Fraunhofer ITEM.

About eight percent of the population worldwide suffer from immune-mediated diseases. Almost any organ or tissue can be affected. In most cases, immune-mediated diseases are treated symptomatically with drugs that non-specifically suppress the patient’s immune system. Therapies that eliminate the cause of the disease and, ideally, are individualized are hardly available at present. There is a great need for research, both on pathophysiological issues and on potential therapeutic targets, and Fraunhofer ITEM is addressing this need.

 

The development, formulation, and mode of delivery of anti-infective substances are current research topics at the institute. The expertise in formulation development is being further expanded and the development and production of anti-infectives for inhaled administration as drug aerosols is being pushed. As far as bacterial infections are concerned, Fraunhofer ITEM has a special focus on the development of manufacturing processes for bacteriophages – in this field the institute is at the cutting edge. Fraunhofer ITEM researchers produce phages as investigational medicinal products and establish models for safety and efficacy testing.

 

Fraunhofer ITEM has many years of expertise in immunotoxicology and immunopharmacology, centered on the development of biopharmaceuticals and advanced therapy medicinal products (ATMPs) in addition to mechanistic research. The focus here is on diseases of the lungs and airways – especially asthma, chronic obstructive pulmonary disease (COPD), fibrotic lung diseases, allergies, and infections. For the investigation of immunomodulatory substances and ATMPs, the institute is further developing in-vitro models, innovative testing strategies, and endpoints in toxicity studies. Human organ models and materials from patients play a pivotal role in this context to enable an even better pharmacological and toxicological understanding of the immune mechanisms relevant to humans.

Development of anti-infective drugs

Urgently needed drug substances against respiratory infections and new preclinical infection models are being developed in research collaborations, for example in the German-Australian iCAIR® consortium. The formulation and mode of delivery of anti-infective substances is also a research topic of current interest at the institute. The competence in formulation development, therefore, will be further expanded and the development and production of anti-infectives for inhaled administration as drug aerosols will be pushed.

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Mimicking infections in lung slices for efficacy testing of drugs: Due to the proximity to the Hannover Medical School, Fraunhofer ITEM researchers in Hannover have direct access to human lung tissue from patients who have undergone surgery, can prepare viable lung slices from this tissue and cultivate these in the laboratory.

Manufacturing bacteriophages to fight bacterial infections

As far as bacterial infections are concerned, Fraunhofer ITEM has a special focus on the development of manufacturing processes for bacteriophages – in this field the institute is at the cutting edge. Fraunhofer ITEM researchers produce phages as investigational medicinal products and establish models for safety and efficacy testing.

Early detection and individualized treatment of immunological diseases

© Fraunhofer ITEM, Ralf Mohr
The focus is on human organ models and patient materials (here: precision-cut lung slices) in order to further improve the pharmacological and toxicological understanding of human-relevant immune mechanisms.

About eight percent of the population worldwide suffer from immune-mediated diseases. Almost any organ or tissue can be affected. In most cases, immune-mediated diseases are treated symptomatically with drugs that non-specifically suppress the patient’s immune system. Therapies that eliminate the cause of the disease and, ideally, are individualized are hardly available at present. There is a great need for research, both on pathophysiological issues and on potential therapeutic targets.

Fraunhofer ITEM has many years of expertise in immunotoxicology and immunopharmacology, centered on the development of biopharmaceuticals and advanced therapy medicinal products (ATMPs) in addition to mechanistic research. The focus here is on diseases of the lungs and airways – especially asthma, chronic obstructive pulmonary disease (COPD), fibrotic lung diseases, allergies and infections. For the investigation of immunomodulatory substances and ATMPs, Fraunhofer ITEM is further developing in-vitro models, innovative testing strategies and endpoints in toxicity studies. Human organ models and materials from patients play a pivotal role in this context to enable an even better pharmacological and toxicological understanding of the immune mechanisms relevant to humans. 

Immunology and infection research: recent projects and highlights

 

Immunology

Learn more about our recent projects in the field of immunology.

 

Fraunhofer Attract project »IMMUNITY – Designer immune cells«

In the project “IMMUNITY – designer cells: novel immune cell platforms for health research” induced pluripotent stem cells (iPSCs) are investigated. The researchers also intend to develop new manufacturing processes for various fully standardized immune cell products and cell-based immunotherapies. 

 

Cyclosporin A: potent antiviral effects in preclinical models of SARS-CoV-2 infection

In drug research for COVID-19 treatment the immunophilin inhibitor cyclosporin A (CsA) was used for the investigation of the antiviral and anti-inflammatory efficacy in human precision-cut lung slices (PCLSs). 

Isolated perfused rat lung (IPL)

The ex-vivo model of the isolated perfused rat lung (IPL) enables the investigation of aerosol droplet absorption.

Project iGUARD

In the iGUARD Projekt a team of researchers is developing RNA-based therapeutics for treating viral diseases. The project is assist by the German Federal Agency for Disruptive Innovation (SPRIND).

Controlling antibiotic-resistent pathogens

Effective new strategies for the fight against resistant pathogens are urgently needed – in particular for treating lung infections. 

iCAIR® consortium

Urgently needed agents against respiratory infections and novel preclinical infection models are being developed in research collaborations, such as the German-Australian iCAIR® consortium. 

 

Production of bacteriophages

Learn more about the intriguing projects PhagoFlow and Phage4Cure.

 

PCLS for drug development

Fraunhofer ITEM scientists use viable human lung slices to develop drugs for COVID-19 treatment.

Project archive

Here you can find more projects sorted by our research and development competences. 

Publications

  • Chen, F., Elgaher, W. A. M., Winterhoff, M., Büssow, K., Waqas, F. H., Graner, E., Pires-Afonso, Y., Casares Perez, L., de la Vega, L., Sahini, N., Czichon, L., Zobl, W., Zillinger, T., Shehata, M., Pleschka, S., Bähre, H., Falk, C., Michelucci, A., Schuchardt, S., Blankenfeldt, W., Hirsch, A. K. H., Pessler, F. (2022). "Citraconate inhibits ACOD1 (IRG1) catalysis, reduces interferon responses and oxidative stress, and modulates inflammation and cell metabolism." Nature Metabolism [Epub ahead of print]. doi: 10.1038/s42255-022-00577-x - Open Access
  • Färber, I., Kruger, J., Rocha, C., Armando, F., von Kockritz-Blickwede, M., Pohlmann, S., Braun, A., Baumgartner, W., Runft, S., Kruger, N. (2022). Investigations on SARS-CoV-2 Susceptibility of Domestic and Wild Animals Using Primary Cell Culture Models Derived from the Upper and Lower Respiratory Tract. Viruses 14(4). doi: 10.3390/v14040828 https://www.mdpi.com/1999-4915/14/4/828 - Open Access
  • Friedrich, M., Pfeifer, G., Binder, S., Aigner, A., Vollmer Barbosa, P., Makert, G. R., Fertey, J., Ulbert, S., Bodem, J., Konig, E. M., Geiger, N., Schambach, A., Schilling, E., Buschmann, T., Hauschildt, S., Koehl, U., Sewald, K. (2022). Selection and Validation of siRNAs Preventing Uptake and Replication of SARS-CoV-2. Front Bioeng Biotechnol 10: 801870. doi: 10.3389/fbioe.2022.801870 https://www.frontiersin.org/articles/10.3389/fbioe.2022.801870/full  - Open Access
  • Heratizadeh, A., Roesner, L. M., Traidl, S., Moitinho-Silva, L., Ellinghusen, B., Rodriguez, E., Harder, I., Sapak, M., Weidinger, S., Badorrek, P., Hohlfeld, J. M., Werfel, T. (2022). Basic skin therapy effects on skin inflammation and microbiome composition in patients with atopic dermatitis after challenges with grass pollen. Journal of the European Academy of Dermatology and Venereology [Epub ahead of print]. doi: 10.1111/jdv.17966 https://onlinelibrary.wiley.com/doi/10.1111/jdv.17966
  • Herrera, V. L. M., Walkey, A. J., Nguyen, M. Q., Gromisch, C. M., Mosaddhegi, J. Z., Gromisch, M. S., Jundi, B., Lukassen, S., Carstensen, S., Denis, R., Belkina, A. C., Baron, R. M., Pinilla-Vera, M., Mueller, M., Kimberly, W. T., Goldstein, J. N., Lehmann, I., Shih, A. R., Eils, R., Levy, B. D., Ruiz-Opazo, N. (2022). A targetable 'rogue' neutrophil-subset, [CD11b+DEspR+] immunotype, is associated with severity and mortality in acute respiratory distress syndrome (ARDS) and COVID-19-ARDS. Scientific Reports 12(1): 5583. doi: 10.1038/s41598-022-09343-1 https://www.nature.com/articles/s41598-022-09343-1  - Open Access
  • Runft, S., Farber, I., Kruger, J., Kruger, N., Armando, F., Rocha, C., Pohlmann, S., Burigk, L., Leitzen, E., Ciurkiewicz, M., Braun, A., Schneider, D., Baumgartner, L., Freisleben, B., Baumgartner, W. (2022). Alternatives to animal models and their application in the discovery of species susceptibility to SARS-CoV-2 and other respiratory infectious pathogens: A review. Veterinary Pathology [Epub ahead of print]: 3009858211073678. doi: 10.1177/03009858211073678 https://journals.sagepub.com/doi/10.1177/03009858211073678
  • Sauerhering, L., Kuznetsova, I., Kupke, A., Meier, L., Halwe, S., Rohde, C., Schmidt, J., Morty, R. E., Danov, O., Braun, A., Vadasz, I., Becker, S., Herold, S. (2022). Cyclosporin A Reveals Potent Antiviral Effects in Preclinical Models of SARS-CoV-2 Infection. American Journal of Respiratory and Critical Care Medicine [Epub ahead of print]. doi: 10.1164/rccm.202108-1830LE https://www.atsjournals.org/doi/10.1164/rccm.202108-1830LE  - Open Access
  • Wienhold, S.-M., Brack, M. C., Nouailles, G., Krishnamoorthy, G., Korf, I. H. E., Seitz, C., Wienecke, S., Dietert, K., Gurtner, C., Kershaw, O., Gruber, A. D., Ross, A., Ziehr, H., Rohde, M., Neudecker, J., Lienau, J., Suttorp, N., Hippenstiel, S., Hocke, A. C., Rohde, C., Witzenrath, M. (2022). Preclinical Assessment of Bacteriophage Therapy against Experimental Acinetobacter baumannii Lung Infection. Viruses 14(1): 33. doi: 10.3390/v14010033 https://www.mdpi.com/1999-4915/14/1/33  - Open Access