Research group We characterize how human B cells in circulation and tissues are affected by underlying disease.
Translational B cell immunology: Activation of the humoral immune system and subsequent production of neutralizing antibodies is a key player for host defense against microbial infections. Our overall research focus is to characterize how human B cells in circulation and tissues are affected by underlying disease, and how this information can be used to develop recombinant antibody-based treatments against virus infections.
Mattias Forsell started his career in experimental HIV vaccine development. However, making a vaccine towards this virus, that mutates quickly, turned out to be difficult and Mattias wanted to find out why. Therefore, he decided to transition to fundamental research to try to decipher how the immune system recognizes and responds to viral spike proteins. These studies were mostly done in small animal models and focused on B cells. These cells can produce specific antibodies against viral spike proteins upon infection or vaccination and play a central role in the immune response.
When Mattias joined Umeå University as a group leader in 2015, he built up a new laboratory and established many collaborations within the hospital to study the human immune response to different viruses. Before the outbreak of the COVID-19 pandemic, the focus of his research was a combination of basic and applied B cell immunology, with emphasis on hantavirus infections (leading to “sorkfeber”) and B cell function in lymphoid tissues. For this purpose, much of his first years at Umeå University were spent on building a network of clinicians with a similar interest in translational research.
As a consequence, the transition to COVID-19 research came naturally. Mattias’s research team initially developed a sensitive ELISA for Region Västerbotten to detect SARS-CoV-2 antibodies in individuals that had recovered from the disease. As part of a Vinnova grant, this method has now been combined with a home sampling device to meet the logistical challenges of detecting the spread of COVID-19 in a rural region, such as Västerbotten.
In addition, the research team of Mattias Forsell is part of a major effort from the Department of Clinical Microbiology to study different aspects of COVID-19. This so called Covum effort is headed by Johan Normark and has recruited over 400 individuals in the early phase of COVID-19 with long-term sampling at regular intervals. The consortium members are using these samples to better understand the SARS-CoV-2 virus, the acute disease COVID-19, and why some individuals have persistent symptoms after infection: long COVID. It is also still not understood why the virus causes destructive inflammation in some individuals, but data generated by researchers at Umeå University and elsewhere demonstrate that immunological memory to SARS-CoV-2 often develops as expected. However, the study has also generated some unexpected findings and the samples collected in the Covum study will be a valuable asset for Umeå University and Region Västerbotten for years to come.
As a continuation of Covum and through a generous grant from Knut and Alice Wallenberg, Mattias Forsell and collaborators will now try to understand how mRNA vaccines trigger the immune system and study the vaccine responses on a molecular level. They will also determine the potency and longevity of vaccine responses in study participants from several regions of Sweden. This information can be used to decide if and when a booster dose is required. “Similarly to Covum, our vaccine studies are made possible through great collaboration between our pre-clinical laboratory and the Clinical Research Center at NUS”, says Mattias. The studies are part of a clinical trial, headed by Johan Normark and Clas Ahlm, and will report their findings directly to Läkemedelsverket and Folkhälsomyndigheten.
Safe to say, 2020 was an interesting year for someone that studies the immunology of virus infections. For his future research plans, Mattias recently received both a consolidatory grant from the Swedish Research Council and funding from Knut and Alice Wallenberg for detailed studies of vaccination. Mattias Forsell is currently looking to strengthen his research team with a postdoc. If you are interested to study the immune response after vaccination and would like to work with the beautiful set of samples that are available in his laboratory, you should contact Mattias.
We focus on basic and applied human B cell immunology and pursue our research in close collaboration with the Region Västerbotten and the University Hospital of Northern Sweden. This translational setting allows us to study primary immune cells in blood and tissues from healthy individuals and selected patient groups. Currently, our projects focus on hantavirus and HIV-1 infections, influenza vaccination and tonsillar hypertrophy.
Modulation of humoral immunity during hemorrhagic fever with renal syndrome (HFRS) and development of novel antiviral therapeutics. The purpose of the project is to contribute towards the development of novel antiviral therapy against human hantavirus infections. Umeå is an endemic area for infections with the Puumala-strain hantavirus and therefore one of the few places in the world where it is possible to perform translational studies of immune responses and pathogenesis to the infection. Specifically, we study how the hantavirus infection affects the humoral immune system and the development of antiviral B cells, and utilize this information to develop a potential treatment for hantavirus-induced HFRS. This project is part of the international Prometheus Center for Excellence in Translational Research (U19 AI142777), funded by NIAID, NIH, USA.
Understanding the impact on underlying HIV-1 disease on vaccine-induced B cell responses. This project specifically aims to reveal if current influenza vaccination regimens is sufficient to generate potent and longitudinal immunity to influenza in HIV-1 patients, and to understand if immune memory formation is affected by the underlying disease. To achieve this, we dissect the polyclonal B cell population into antigen-specific sub-populations. This allows us to study longitudinal development of influenza specific B cells from the initial activation to long-term B cell memory formation and maintenance in HIV-1 patients after the annual influenza vaccination.
The life and death of adaptive humoral immunity: from tissue to circulation, and back. Adaptive immune responses in humans are generally investigated by characterization of the peripheral B cell compartment in circulation. Here, we focus on basic investigations of adaptive B cell responses to gain a better understanding of how immune reactions in secondary lymphoid organs is reflected by an altered B cell compartment in the circulation of patients.
If you are interested in joining our team as postdoc, PhD or undergraduate student, please contact Mattias Forsell.
2. Vaccines and vaccination