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.

Research in the field of infectious diseases became particularly important with the outbreak of the SARS-CoV-2 pandemic. At Fraunhofer ITEM, funding programs of the Fraunhofer-Gesellschaft and the German Federal Ministry of Education and Research as well as contract research commissioned by industry helped to get numerous projects up and running within a very short time. The aims were to better understand the infectivity and transmissibility of SARS-CoV-2, to develop corona-specific active and passive vaccines and to evaluate the safety and efficacy of therapeutics for treating COVID-19. The findings from a broad range of research projects performed at Fraunhofer ITEM have made a valuable contribution to the fight against the corona pandemic and help to generate knowledge for potential future pandemics. For example, researchers of the Division of Pharmaceutical Biotechnology managed to manufacture neutralizing antibodies against SARS-CoV-2 as an investigational medicinal product in record time: the IMP was advanced to the stage of clinical testing in less than seven months.

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

Drug repurposing

In the fight against the SARS-coronavirus-2, drug repurposing has proven a suitable fast track to making effective therapeutics available. Learn more about the projects DRECOR and RENACO.

 

Immunology

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

Fraunhofer CIMD

In view of the importance of immunological diseases, the Fraunhofer-Gesellschaft established the Cluster of Excellence Immune-Mediated Diseases – Fraunhofer CIMD – in 2017, with Fraunhofer ITEM as one of the core institutes.

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.

Aerosols in the pandemic

Aerosols and the risk of airborne infection with SARS-CoV-2 have been addressed in our projects CoClean-up, AVATOR and QUELLE. 

Isolated perfused rat lung (IPL)

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

RSV-mediated asthma

Fraunhofer ITEM scientists have established a model that mimics the RSV infection ex vivo in viable human lung tissue. This model is now being used to develop novel therapeutic approaches aimed at preventing RSV-mediated asthma.

BEAT-COVID

In the BEAT-COVID project, researchers have developed novel therapeutic strategies and platform technologies to enable rapid and targeted development of new drugs against as yet unknown pathogens.

 

PCLS for drug development

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

Development of novel COVID-19 therapeutics

Scientists have set up a “screening pipeline” for the development of novel COVID-19 therapeutics.

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