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Infection models in virus research

The main aim of the Platform Infection Models is to establish and to continuously develop various models for infection research while steadily considering the 4R principles (replacement, reduction, refinement, responsibility). Depending on the scientific question, different models may be considered for infection research. These models include both in-vivo models in non-human primates (NHP) as well as ex-vivo models with primary cell cultures. Established models are used for infection studies and the testing of antiviral substances and vaccines.

Immortalized cell cultures

Immortalized cell lines are frequently used in infection research and are suitable for fundamental studies on pathogen-host interactions and for preliminary testing of antiviral substances. Various cell lines are also used for the isolation, propagation, and titration of viruses.

However, their applications are limited, especially when studying the immune response of humans or animals to a viral infection. The complex interaction between the different components of the immune system cannot yet be fully replicated in cell culture systems.

Moreover, the diversity of cell types is lost in immortalized cell lines, and changes in the expression patterns of cellular proteins can occur. The cell physiology can change to such an extent that it leads to cell culture artifacts, making the in-vitro results not transferable to the living organism. Therefore, cell cultures do not sufficiently reflect the in-vivo situation of specific organs. For more in-depth analyses of interactions between pathogens and hosts, it is inevitable to use more complex models that ideally copy the situation within the living organism.

Primary cell cultures

Primary cell cultures reflect the in-vivo situation of selected organs very well; depending on the culture, the organ-specific cellular structure remains fully intact. Unlike immortalized cells, primary cells are unaltered and retain their specific physiology and function. Since primary cell cultures can be obtained from organ samples such as biopsy material or freshly deceased organisms, no experimental animals are needed to produce these cultures. Therefore, primary cell cultures offer an alternative to infection studies in animal models, contributing to the reduction of the number of experimental animals.

The main focus of the Platform Infection Models lays on primary cultures of the respiratory tract. Especially precision-cut lung slices (PCLS) represent an ex-vivo model for studying respiratory diseases. They allow the examination of the general susceptibility of lung cells to specific pathogens, the identification of target cells, and the testing of antiviral agents in a setting that closely mimics the conditions of the lung.

The SARS-CoV-2 pandemic has made it clear that new infectious diseases can spread at any time and pose a serious threat to human health. The timely development and testing of new drugs and vaccines play a crucial role in combating and preventing infectious diseases. The interaction between pathogen and host, as well as the host's complex immune response to an infection or vaccination, cannot yet be fully studied in cell culture or alternative models. Therefore, for specific questions regarding the spread and control of infectious diseases, we will continue to rely on animal testing for the time being.

In vivo models possess the highest level of complexity and are particularly suited for questions regarding the transmission, pathogenesis, treatment, and immune response of infectious diseases. For ethical and animal welfare reasons, in-vivo models may only be used if the scientific knowledge is not yet sufficiently known, if they offer a benefit to human or animal health, and if the findings cannot be obtained through a less complex model.

Due to their close evolutionary relationship to humans, primates are highly suitable for studying and understanding various aspects of infectious diseases in humans such as implies transmission paths, pathogenesis, therapeutic approaches or the testing of new immunization strategies and vaccines for antiviral prophylaxis. The choice of primate model depends on the specific research question and the pathogen to be analyzed. Rhesus macaques, long-tailed macaques and common marmosets are among the most frequently used animal models. The experimental units at DPZ facilitate the conduct and analysis of infection experiments with biological and genetically modified pathogens classified under biosafety levels 1-3, in accordance with the regulations of the Biological Agents Ordinance, the Specified Animal Pathogens Ordinance, and the Genetic Engineering Act.

Among the established models in rhesus and cynomolgus monkeys are the SIV model for studying HIV, research on new therapeutic options with adeno-associated viruses, and infection models for various respiratory viruses such as respiratory syncytial virus, influenza A viruses, and SARS-CoV-2.
Routine sampling is mainly done via collection of blood samples, swabs samples, urine samples, bronchoalveolar la­vage fluid and, depending on the research questions and pathogen, bone marrow puncture, collection of cerebrospinal fluid and lymph node biopsies.

Selected publications

  • Genetic barrier to resistance: a critical parameter for efficacy of neutralizing monoclonal antibodies against SARS-CoV-2 in a nonhuman primate model.

    J Virol. 2024 Jul 23;98(7):e0062824 - DOI -
  • Filamentous fungus-produced human monoclonal antibody provides protection against SARS-CoV-2 in hamster and non-human primate models.

    Nat Commun. 2024 Mar 14;15(1):2319 - DOI -
  • 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. 2022 Apr 16;14(4):828 - DOI -
  • The Upper Respiratory Tract of Felids Is Highly Susceptible to SARS-CoV-2 Infection.

    Int J Mol Sci. 2021 Sep 30;22(19):10636 - DOI -
  • Synergistic inhibition of SARS-CoV-2 cell entry by otamixaban and covalent protease inhibitors: pre-clinical assessment of pharmacological and molecular properties.

    Chem Sci. 2021 Aug 26;12(38):12600-12609 - DOI -