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Pandemic Preparedness Capabilities

Testing BSL3 Biomedicum capabilities and more


PI(s)/Head responsible for the resource:

Antonio Rothfuchs

Host organisation(s):

Karolinska Institutet

Resource description:

The Biosafety Level 3 (BSL3) research infrastructure at Biomedicum has been seamlessly integrated into the PLP capability of SciLifeLab (see details on the previous project grant). The facility offers specialised platforms in BSL3 for high-throughput (HTP) drug screening and pathogen aerobiology. The facility also leads the Swedish BSL3 Network (SB3N), a first-of-kind network for academic BSL3 laboratories in Sweden to interact with each other. The project has 3 aims divided into 3 work packages (WPs), and uses the pandemic pathogen Monkeypox virus (MPXV) as a demonstrator.

The Aims of the project are to:

  1. Test the access pipelines for MPXV isolates from the latest outbreak (WP1)

  2. Test the workflows of the specialised platforms build in BSL3 Biomedicum (WP2)

  3. Perform a comprehensive consequence analysis of identified bottlenecks (WP3)

There is an overwhelming consensus among the academic members of SB3N that Swedish SARS-CoV-2 strains were difficult to obtain during the COVID-19 pandemic. In WP1 we will investigate this by requesting access to Swedish MPXV isolates from the 2022 outbreak. Isolates will be requested from FoHM and from laboratories in the healthcare regions that have PLP projects. We will map hurdles in delivery of isolates. In WP2 we will test the ability of BSL3 Biomedicum to adapt MPXV to its high-end platforms for HTP antiviral screening and pathogen investigation in aerosols. These activities support both PLP and biodefense applications. In WP3 we will perform a consequence analysis to evaluate workflows in access to isolates and in the adaptation of our specialised platforms to MPXV. We will be supported by FoHM in this process to systematically analyse pros, cons, and challenges. Finally, risk mitigation measures will be proposed and communicated to counter hurdles in access to strains, and to counter choke points in our established high-end platforms. This will prepare us when we shift gears again to wartime/early pandemic activities.

Research findings:

Our program has provided BSL3 access support to many researchers. Since 2020, 95 users have been trained in our BSL3 facility and its platforms. Users were supported with training and method development, they received access to pathogen strains and to equipment. BSL3 Biomedicum is today a high-end hub for research on RG3 pathogens with tuned workflows, experienced technical staff, with a pathogen biobank that includes Swedish SARS-CoV-2 and Monkeypox isolates, and cutting-edge equipment.

We became the first BSL3 in Sweden with specialized capabilities. Our capability for screening drug libraries in BSL3, established together with precision medicine experts at SciLifeLab and CBCS, has delivered a scalable, imaging-based assay to test antivirals. It was developed for SARS-CoV-2 and can be adapted to Monkeypox virus. A related, scalable assay was developed that reports on cell death after virus infection. Our capability to study pathogens in aerosols is world-unique. With the Swedish Environmental Epidemiology Center (REPLP1-007, PLPTEST:G019) we have used tools from this capability for sampling initiatives in healthcare. We have delivered a method based on electrostatic air sampling to detect airborne SARS-CoV-2 by culture and molecular assay (PCR). It has been successfully used to detect SARS-COV-2 in air from hospital rooms occupied by COVID-19 patients. The assay was refined with visualization of virus by confocal microscopy in the same sample and successfully used to detect infectious SARS-CoV-2 in cough from COVID-19 patients. Our aerobiology capabilities were also applied in the PLP project in nursing homes (PLP2-004, PLPTEST:G014) where we investigated the presence of respiratory viruses and measured air quality. We sampled air and surfaces from shared spaces where nursing-home residents congregate, and monitored the air for particulate matter, CO2, humidity and temperature. Using sensitive molecular detection assays developed with National Pandemic Center we detected different respiratory viruses in the environment. These measurements will be combined with records of respiratory illness in the residents to see if they can be used in a predictive model.

We created the Swedish BSL3 Network (SB3N), a network for BSL3 managers, technicians and users to share experiences, knowledge and methods. It is also a meeting place for university BSL3 laboratories to connect with government BSL3 laboratories and with microbiology units in hospitals. We have mapped BSL3 resources in different Swedish universities so that researchers know which facility to approach for specific help with their experiments. We have partnered with a similar network in Canada with whom we can share experiences. Before SB3N, Swedish facilities worked alone without talking to each other. Now we can work together, share methods, equipment, best practices, pathogen strains, and avoid unnecessary duplication of experiments and expensive equipment.

Impact on prepardness for future pandemics:

Before SB3N, facilities worked alone without cross-pollination. Today we have a forum to meet and talk with each other, with government BSL3s, with clinical microbiology laboratories in the Regions, and with a similar network in Canada. These interactions are projected to reduce the reaction time of the Swedish academic sector in the next pandemic, and improve the sharing of workflows, methods and pathogen strains during also in-between pandemics.

The increased availability of BSL3 technicians in our facility, and the introduction of equipment and new methods, have sustained the rollout of BSL3 research beyond the pandemic. By supporting BSL3 research our program has promoted the creation of a group of highly-trained researchers (technicians and users) and sustained the continued development of methods in BSL3. These capabilities are very useful to braise future pandemic threats. We will not have to re-build our skills and capabilities from zero when facing off the next pandemic.

Contact information:

Marianna Tampere
Coordinator Swedish BSL3 Network
Email: marianna.tampere@ki.se

Antonio Gigliotti Rothfuchs
BSL3 Director
Email: antonio.rothfuchs@ki.se