Innovative use of drug candidates for respiratory tract infections

© Fraunhofer ITEM, Ralf Mohr
The isolated perfused lung is a model for the investigation of airborne substances. It provides an alternative to animal models in the spirit of the 3Rs.

The SARS-CoV-2 pandemic made it clear to all of us how seriously respiratory infections can affect people’s health. The Fraunhofer “Infection and Immunology” research group conducts various projects to investigate the efficacy of unique drug candidates for viral and bacterial respiratory infections. In the past year, it has succeeded in developing and testing new viral inhibitor candidates.

Researchers at Fraunhofer ITEM and the Hannover Medical School MHH have jointly pursued an innovative approach: Together, they have developed an RNA-based active substance to treat human parainfluenza virus (HPIV3) and have also tested it successfully in a preclinical setting. First, they identified potentially effective RNA candidates in cell culture models. Using an in-vitro approach, the researchers demonstrated a significant reduction in viral load in HPIV3-infected LLC-MK2 cells with some of these candidates. The most promising candidate also demonstrated efficacy in a more complex, human tissue system: human precision-cut lung slices (PCLS). To increase efficacy at the infection site, an RNA formulation was developed specially for administration by inhalation. The RNA was packaged in lipid nanoparticles (LNPs) and various LNP formulations were tested after administration by inhalation in isolated perfused rat lungs. The German Federal Agency for Disruptive Innovation (SPRIND) funded the project through a national research competition.

Since efficacy testing for clinical development of a medicinal product has to be done in an animal model, the researchers at Fraunhofer ITEM developed an infection model in cotton rats. In line with the 3R principles (reduction, refinement, replacement of animal testing), PCLS were first generated from cotton rats and treated similarly to human PCLS. A successful reduction in viral load was observed, which meant that cotton rats could be treated with inhaled LNP-packaged RNA for the first time. The next development steps include toxicological tests.

Another project also involves an inhaled treatment for viral infections. Together with OM Pharma, researchers at Fraunhofer are investigating the immunological response of virus-infected and non-infected murine PCLS or human cells following ex-vivo and in-vitro treatment with the active substance OM-85. The active substance was also tested in isolated perfused lungs following administration by inhalation. This made it possible to plan the next steps toward developing a treatment with inhaled OM-85.


Franziska Dahlmann

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Dr. Franziska Dahlmann

Manager of the Working Group on Infection and Immunology

Phone +49 511 5350-416