Sara Gredmark Russ group - Viruses and their interactions with the immune system

The research in our group lies within the area of immunology, with the main focus on viruses and their interactions with the immune system.

Group photo three women.
The Sara Gredmark-Russ research group at CIM, MedH. Photo: Tyler Sandberg

About our research

Viral infections can cause a number of different acute and chronic conditions. The approaches to treat these conditions are limited, and for many viral infections, there are no alternatives at all. Our research focuses on advancing the knowledge in the basic principles of the immune response to viral infections in humans. Our long-term goal is, aside from gaining knowledge in the basic functions of the human immune system, to contribute to the development of new diagnostics, treatment, and vaccination strategies for viral infections.

Studies of TBEV virus

One of the main subjects of our research is tick-borne encephalitis virus (TBEV). TBEV is a member of the flavivirus family, and is transferred to humans from ticks. TBEV is the causative agent of tick-borne encephalitis (TBE). One major problems with TBE is the risk for long lasting neurological sequelae. TBE is an emerging disease and has become a growing health challenge in endemic areas. The only effective protection against TBE is properly timed vaccination, before the exposure to TBEV-infected ticks.

The TBE disease progression in humans. Illustration: Servier Medical Art

Despite the fact that vaccination against TBE is increasing in the at-risk population in Sweden, the numbers of patients suffering from TBE have also been increasing over the last decade. In addition, over the last years a number of vaccine failures have been reported.

Even though TBE has become an important public health concern, the underlying basis for the development of encephalitis in TBEV infection remains undefined, and there are only a few studies addressing the mechanism of disease development.

Sara Gredmark-Russ about TBE in the podcast Medicinvetarna (in Swedish)

TBE disease progression

Group leader

Sara Gredmark Russ

Group leader, MD, PhD

Sara is a Medical Doctor, Karolinska Institutet, 2001. PhD in Experimental medicine, Center for Molecular Medicine (CIM) at KI, 2005, working in the area of immunology and virology. She is also Post Doctoral fellow in the laboratory of Hidde Ploegh, at the Whitehead Institute at MIT 2005-2008, working with immunology, biochemistry and virology. Sara is Associated professor at Karolinska Institutet since 2019 and Infectious Diseases Doctor at the Infectious Disease Clinic at the Karolinska University Hospital.

Group members

Renata Varnaite

Doctoral Student, MSci

Renata obtained her MSci degree in Biochemistry from the University of St Andrews before moving to Sweden. Her degree involved a 1-year-long research placement at the laboratory of Jonathan Stoye at Francis Crick Institute, London, where she studied evolution of antiretroviral gene Fv1. During her Master’s project Renata focused on developing a DNA vaccine against Foot and Mouth Disease Virus at Martin Ryan lab in St Andrews. She continues her education in virology and immunology at Karolinska Institutet since 2016 with the focus on human immune system responses to tick-borne encephalitis virus infection.

Núria Mayola Danés

Doctoral Student, MSci

Núria has a background in neuroscience and worked as an intern at Jonathan Gale’s lab at the UCL Ear Institute in London before moving to Sweden in 2019. She obtained her MSc at Karolinska Institutet with a focus in immunology. She completed her Master’s project on the study of the process of NK cell education at the Höglund laboratory.  

Núria joined Sara Gredmark Russ’ group in 2021 to start her PhD on tick-borne encephalitis from both an immunological and virological standpoint.  

Open positions

We always want to get in touch with talented potential co-workers. If you are interested in doing research within our group, as a degree project or as a researcher, please contact the Group leader Sara Gredmark Russ.

Projects

Characterization of the immune response during the natural course of tick-borne encephalitis virus (TBEV) infection in humans

In this project, we utilize advanced flow cytometry and other immunology methods, in order to characterize the kinetics and profile of innate and adaptive immune responses during TBE disease and TBE vaccination. Our overall goal is to translate our findings for the improvement of diagnostic tools, vaccine strategies and treatment of patients.

Identification of human cellular proteins and factors required for TBEV entry and replication

This project aims to identify human cellular proteins that are essential for TBEV infection, which could serve as novel therapeutic targets for TBE treatment. We utilise a genome-wide haploid genetic screen, a cutting-edge technology that allows rapid and sensitive identification of host factors utilised by pathogens for their entry and replication. This technique will be combined with deep sequencing and advanced bioinformatics analysis to identify host proteins needed for TBEV infection.

Immune cells in the central nervous system during viral infections

In healthy conditions, lymphocytic trafficking into the CNS is tightly controlled by the blood brain-barrier (BBB), but under inflammatory conditions, circulating lymphocytes and monocytes/macrophages can cross the BBB easily and gain access to CNS compartments, potentially leading to pathology. This project aims to characterize the infiltrating immune cell subsets within the cerebrospinal fluid and compare the subsets with peripheral blood. Additionally, we utilize in vitro BBB models to study the transmigration capability of immune cells during neurotropic viral infections. 

Characterization of the immune response during SARS-CoV-2 (COVID-19) infection in humans

Recently, with the first case in 2019, SARS-Cov-2 (COVID-19), has emerged, causing severe respiratory disease, and having a significant burden on the health care system. We have set up a similar approach as for TBE to study SARS-Cov-2 in order to characterize the kinetics and profile of the adaptive immune responses during COVID-19 infection.

Keywords

virus, infection, T cells, immunology, host response, central nervous system

Research support

Swedish Research Council

MIMS Clinical Research Fellows Programme

Center of Innovative Medicine, Region Stockholm

Region Stockholm

Karolinska Institutet

Selected publications

SARS-CoV-2-specific humoral and cellular immunity persists through 9 months irrespective of COVID-19 severity at hospitalisation.
Sandberg JT, Varnaitė R, Christ W, Chen P, Muvva JR, Maleki KT, García M, Dzidic M, Folkesson E, Skagerberg M, Ahlén G, Frelin L, Sällberg M, Eriksson LI, Rooyackers O, Sönnerborg A, Buggert M, Björkström NK, Aleman S, Strålin K, Klingström J, Ljunggren HG, Blom K, Gredmark-Russ S,
Clin Transl Immunology 2021 ;10(7):e1306
PMID: 34257967 

Shedding of infectious SARS-CoV-2 by hospitalized COVID-19 patients in relation to serum antibody responses.
Glans H, Gredmark-Russ S, Olausson M, Falck-Jones S, Varnaite R, Christ W, Maleki KT, Karlberg ML, Broddesson S, Falck-Jones R, Bell M, Johansson N, Färnert A, Smed-Sörensen A, Klingström J, Bråve A
BMC Infect Dis 2021 May;21(1):494
PMID: 34044758 

Expansion of SARS-CoV-2-Specific Antibody-Secreting Cells and Generation of Neutralizing Antibodies in Hospitalized COVID-19 Patients.
Varnaitė R, García M, Glans H, Maleki KT, Sandberg JT, Tynell J, Christ W, Lagerqvist N, Asgeirsson H, Ljunggren HG, Ahlén G, Frelin L, Sällberg M, Blom K, Klingström J, Gredmark-Russ S
J Immunol 2020 11;205(9):2437-2446
PMID: 32878912 

Magnitude and Functional Profile of the Human CD4+ T Cell Response throughout Primary Immunization with Tick-Borne Encephalitis Virus Vaccine.
Varnaitė R, Blom K, Lampen MH, Vene S, Thunberg S, Lindquist L, Ljunggren HG, Rombo L, Askling HH, Gredmark-Russ S
J Immunol 2020 02;204(4):914-922
PMID: 31924650

Tick-borne Encephalitis Vaccine Failures: A 10-year Retrospective Study Supporting the Rationale for Adding an Extra Priming Dose in Individuals Starting at Age 50 Years.
Hansson KE, Rosdahl A, Insulander M, Vene S, Lindquist L, Gredmark-Russ S, Askling HH
Clin Infect Dis 2020 01;70(2):245-251
PMID: 30843030 

Breadth and Dynamics of HLA-A2- and HLA-B7-Restricted CD8+ T Cell Responses against Nonstructural Viral Proteins in Acute Human Tick-Borne Encephalitis Virus Infection.
Lampen MH, Uchtenhagen H, Blom K, Varnaitė R, Pakalniene J, Dailidyte L, Wälchli S, Lindquist L, Mickiene A, Michaëlsson J, Schumacher TN, Ljunggren HG, Sandberg JK, Achour A, Gredmark-Russ S
Immunohorizons 2018 07;2(6):172-184
PMID: 31022685

NK Cell Responses to Human Tick-Borne Encephalitis Virus Infection.
Blom K, Braun M, Pakalniene J, Lunemann S, Enqvist M, Dailidyte L, Schaffer M, Lindquist L, Mickiene A, Michaëlsson J, Ljunggren HG, Gredmark-Russ S
J Immunol 2016 10;197(7):2762-71
PMID: 27543616

Specificity and dynamics of effector and memory CD8 T cell responses in human tick-borne encephalitis virus infection.
Blom K, Braun M, Pakalniene J, Dailidyte L, Béziat V, Lampen MH, Klingström J, Lagerqvist N, Kjerstadius T, Michaëlsson J, Lindquist L, Ljunggren HG, Sandberg JK, Mickiene A, Gredmark-Russ S
PLoS Pathog 2015 Jan;11(1):e1004622
PMID: 25611738