BSL3 Biomedicum-SciLifeLab Collaborative Platform

PI(s)/Head responsible for the resource:

Antonio Rothfuchs

Host organisation(s):

Karolinska Institutet

Resource description:

The Biosafety Level 3 (BSL3) laboratory is a barrier with advanced work routines, equipment with extra safety measures, manned by highly-qualified personnel (HQP) that perform experiments, introduce technology, and train users. It is essential for research activities on risk-group 3 pathogens and as such to mount a rapid response to new outbreaks. Research activities in BSL3 include pathogen isolation and culture, evaluation of pathogen function and interaction with host cells, establishment of diagnostics and pathogen-detection methods, validation of pathogen inactivation methods, measurement of pathogen half-life on surfaces and in air, drug screening, antimicrobial resistance screening, vaccine testing, and many other infection assays in cells, tissues, or organoids. The BSL3 laboratory is incumbent to Pandemic Laboratory Preparedness (PLP).

This resource involves two separate components:

(1) Inclusion of Karolinska Institutet’s BSL3 facility in Biomedicum as a capability within SciLifeLab’s PLP program.

(2) Establishment of the Swedish BSL3 Network, a platform for BSl3 facilities to share experiences, resources and network.

1. Access to Swedish researchers to a state-of-the-art biosafety level 3 (BSL3) facility

BSL3 Biomedicum in Solna is approved to handle various RG3 pathogens (viruses, parasites and bacteria), including several genetically-modified variants (R-GMM). As part of the PLP program, the facility supports research activities integrated in its capabilities that are available also as a service to users.

Advanced capabilities for Pandemic Preparedness:

The facility has unique capabilities for high-throughput (HTP) screening and for pathogen aerobiology. For HTP, the facility is equipped with pipetting robotics and advanced plate reading to screen compound libraries in BSL3 using an imaging-based approach, and a luminescence-based approach to study cell-cytopathic effects. The HTP capability draws on a close collaboration with SciLifeLab’s CBCS (Chemical Biology Consortium Sweden) infrastructure. For aerobiology, the facility is equipped with a world-unique capability to study the decay of pathogens in aerosol, reliant on a tailored aerosol chamber and air sampling devices. The facility has air sampling methods to detect SARS-CoV-2 in aerosol by culture and molecular methods.

For more information on BSL3 Biomedicum (including information on access, use, full instrument capabilities and contact), please see the dedicated BSL3 facility page.

2. The Swedish Biosafety Level 3 (BSL3) Network

The Swedish BSL3 Network (SB3N) is an open network for Swedish BSL3 facilities, in academia and government (BSL3 Directors, HQPs, and users alike) to come together to share experiences, knowledge, and technology. The network maps Swedish BSL3 capabilities and specialisations, defines joint actions for PLP and provides visibility and outreach for its members. Current members in the network come from 6 different Swedish universities and 1 university hospital. SB3N collaborates with the Canadian Consortium for Academic BSL3 Laboratories (CCABL3) and the Coronavirus Variants Rapid Response Network (CoVaRRNet).

For more information on the BSL3 Network (including information on access, use, and contact), please see the dedicated BSL3 network page.

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
Director, BSL3 Biomedicum
Email: antonio.rothfuchs@ki.se