Clinical Virology and Immunology – Annika Karlsson's research group

Our research goal is to define virus-specific T cell immunity in pregnant women, children, adolescents, adults, elderly, and in human cancer with implications for immunopathogenesis, development and regulation of the immune system, and health. We are the link between immune response and health with an emphasize on chronic HIV and acute respiratory tract viral infections.

Anna Olofsson and Annika Karlsson

Research focus

Our research goal is to define virus-specific T cell immunity in pregnant women, children, adolescents, adults, elderly, and in human cancer with implications for immunopathogenesis, development and regulation of the immune system, and health (Figure 1). We are the link between immune response and health with an empahsize on HIV and SARS-CoV-2 infection.  

By adapting bioinformatics my group has established a system to evaluate virus-specific CD4 and CD8 T cell responses in genetically diverse populations infected with different viral variants.  The work is based on collecting and identifying T cell responses in well characterized patient cohorts from which we conduct genetic typing of the viral population and the patient’s human leukocyte antigen (HLA) class I and II haplotypes (Figure 1). This, the genetic information of the virus and the host, is essential for our evaluation of HLA – epitope – T cell receptor (TCR) specific interactions in relation to different aspects of the of pathogen- and malignancy-specific T cell subpopulations in blood and tissue. Our approach has important implications for our potential to identify correlates for the efficacy of virus-specific T cell responses in relation to human health. Our goal is to guide future treatments and vaccinations strategies in children and elderly by increase our understanding of the cellular prerequisites for development, maintenance, and function of antiviral memory T cells.

Research genre image showing Figure 1. Dissecting antiviral T cell immunity in relation to age, pregnancy, viral infections, cancer, treatment, and clinical health.
Figure 1. Dissecting antiviral T cell immunity in relation to age, pregnancy, viral infections, cancer, treatment, and clinical health. Photo: Annika Karlsson
Common cold gives children immunity against COVID-19
Photo: Getty Images
Research in media

Common cold gives children immunity against COVID-19

Researchers at Karolinska Institutet are now able to show that OC43, one of the coronaviruses that cause common colds, boosts the immune response to COVID-19. The study, which is published in PNAS, could give rise to more tailored vaccine programmes for children and adults.

Publications

Selected publications

Alumni

Carina Pérez, PhD student

Carina defended her PhD in 2011. Part of Carina’s doctoral research was carried out a Gladstone Institutes, University of California, San Francisco together with Prof Douglas Nixon. Today, Carina is Recruitment Consultant at QRIOS Life Science & Engineering, Sweden.

Melissa Norström, PhD student

Melissa defended her PhD in 2012. Part of her doctoral research was carried out at Department of Pathology of the University of Florida College of Medicine together with Prof Marco Salemi. After this she continued as a postdoctoral fellow at Centre for Allogeneic Stem Cell Transplantation (CAST), Department of Oncology and Pathology, KI, Stockholm, Sweden. Currently she is a Consultant in Medical Affairs, Medicine Doctor and CEO of Florebit AB.

Marcus Buggert, PhD student, Postdoctoral Fellow

Marcus defended his PhD in 2014. He was awarded the Sven Gards stipendium for the best PhD thesis in virologi at KI during 2014. He also received international postdoc grant from the Swedish research council 2014 and joined Dr. Michael Betts lab, Department of Microbiology, University of Pennsylvania, PA, USA. In 2017 he returned to KI, Department of Medicine as an Assistant Professor and became group leader in 2019 https://orcid.org/0000-0003-0633-1719.

Johanna Taurianen, PhD student

Johanna defended her PhD in 2016. She continued her studies on viral-associated CD8 and NK cell responses as a Postdoctoral Fellow in Dr. Jonas Klingström group, Department of Medicine, Center for Infectious Medicine – CIM, Karolinska Institutet. Currently, she is working as a Scientist på Anocca AB, Stockholm, Stockholm, Sweden.

Lydia Scharf, PhD student

Lydia defended her PhD in 2020. After graduation Lydia continued her research path as a Postdoctoral Fellow in Group Davide Angeletti, Department of Microbiology and Immunology, University of Gothenburg, Sweden. Lydia is currently investigating B cell responses to COVID19 after infection and vaccination.   

Marion Humbert, Postdoctoral fellow

Marion carried out her postdoctoral projects in the group 2020 – 2022, while being involved in several projects, including investigation of the role of cross-reactive SARS-CoV-2 T cell immunity in relation to age (Karlsson AC, Sci Immunol. 2020; Humbert, PNAS. 2023). Marion is currently a postdoctoral fellow in Prof Johan Sandberg’s group at CIM, KI.

Projects

1. The link between immune response and health in treated HIV-infection

Chronic infection and immunosuppression are important risk factors for many types of cancer. HIV is one chronic infection associated with severe immunosuppression that is only partly reversed by antiretroviral treatment (ART). In an era where HIV-infected individuals require life-long ART to control viral replication it is important to reveal the mechanisms linked to adverse health effects to refine therapeutic interventions, especially in pregnant women, children and adolescence. The CD4 and CD8 T cells which is an important part of the adaptive cellular immune system in both cancer and chronic infection becomes highly dysfunctional during an HIV-infection (Figure 2). This process is usually known as T cell exhaustion. In our projects the goal is to gain insights into how to achieve optimized treatment of HIV in perinatally infected children, pregnant women, adults, and in HIV-associated cancers. Thereby leading the way to better clinical outcomes in HIV infected and uninfected patients.

Genre image showing The importance of T cells in the battle against viral infection and cancer.
Figure 2. The importance of T cells in the battle against viral infection and cancer. During the induction of an antigen-specific T cell response. The HLA-I-peptide complex is recognized by the CD8 T cells while peptides presented by HLA-II are recognized by CD4 T cells. The ability of the host to generate efficient T cell responses are dependent on the epitopes targeted, antigen abundance, and host genetic factors such as HLA type and TCR repertoire. CD4 T cells coordinate immunity and CD8 T cells exert antiviral effector functions. During cancer or a chronic infection, the immune system is not able to clear the antigen, persistent antigen stimulation. Subsequently, the memory T cell repertoire becomes highly dysfunctional. This process is known as T cell exhaustion. Photo: Annika Karlsson

2. T cell immunity during pregnancy and childhood in relation to viral infection, treatment, and health

The severity and clinical profile of many viral infections is affected by age and pregnancy. Studies on qualitative aspects of antiviral cellular immunity in children and pregnant women is outdated calling for new insights into their role for health and immunopathogenesis. Qualitative differences in viral-specific T cell responses may reflect the ability of the host to control virus infections and respond to vaccination.  Pregnancy presents a major challenge for the immune system, where foetal immune tolerance must be upheld while maintaining immune functions. While pregnancy does not increase general susceptibility to infection, it has been shown to increase the risk of severe disease to viral infections (HIV, Coronavirus, Influenza). In this collaborative effort we aim to define T cell immunity in relation to clinical, virological, and bacteriological factors in HIV-infected and HIV uninfected children, pregnant women and their offspring (Figure 1). Our results will provide a rational framework for personalized monitoring and evaluation of antiviral treatment and vaccination strategies for children and pregnant women.

3. The role of cross-reactivity and immune evasion in the control of respiratory viral infections

Our current understanding of T cell immunity against respiratory virus and their viral variants in relation to age is incompletely characterized (Karlsson AC, Sci Immunol. 2020). Infants and young children and elderly are more vulnerable to severe viral infections, particularly to respiratory and enteric viruses, including Coronaviruses (SARS-CoV-2 and the four circulating seasonal coronaviruses), Influenza viruses, and Respiratory syncytial virus, compared to adults. We will provide the scientific community with fingerprints of the memory T cell responses against these common respiratory tract viral infections from childhood until late adulthood (Humbert M, PNAS. 2023). Our overall goal is to understand the role of SARS-CoV-2-specific CD4 and CD8 memory T cell responses in relation to previous exposure to seasonal human coronaviruses (HCoVs), pathogenic viral SARS-CoV-2 variants, and vaccination (Figure 1). Subsequently, based on the level of viral conservation within a targeted epitope we should be able to predict how effective such immune response, naturally or vaccine induced, would be in targeting specific viral variants.

Articles in media

KI:  https://news.ki.se/common-cold-gives-children-immunity-against-covid-19

Läkemedelsvärlden: https://www.lakemedelsvarlden.se/vanligt-forkylningsvirus-skyddar-barn-mot-covid-19/ (only in Swedish)

The Conversation: https://www.gavi.org/vaccineswork/could-common-cold-give-children-immunity-against-covid-our-research-offers-clues

4. The role of virus-specific T cell exhaustion in human cancer

Chronic antigenic stimulation, such as by cancer or viral antigens, invariantly causes T cell exhaustion. HIV is together with human papillomavirus (HPV), Hepatitis B and C viruses (HBV and HCV), and Helicobacter pylori (H. pylori) among the chronic infections related to cancer. T cell exhaustion and immunosuppression is an important risk factor for many types of cancer. To increase the survival rate in invasive cancer novel immune-based treatment options needs to be developed. To obtain more efficient therapy options for cancer in different stages of development, combinational therapies using immune checkpoints inhibitors to enhance antigen-specific T cell responses are a promising option. Our research goal is to combine clinical, immunological, and molecular biology methodology with bioinformatics to characterize the molecular mechanisms of HIV- and HPV-specific T cells in human cancer affecting disease progression and health (Figure 1). Through the study-outline we will gain mechanistic knowledge of viral- and malignancy-specific T cell exhaustion that can be applied in a variety of cancers where immunomodulation can be used to counteract cancer progression.

Collaborations

Current National Collaborations

(*shared supervision of PhD student(s))

  • Karin Pettersson*, MD, PhD. Head of obstetrics. Expertise: Senior Consultant Obstetrics at Karolinska University Hospital.
  • Lars Navér*, MD, PhD Section Manager Neonatal operations. Expertise: Senior Consultant Neonatology and Pediatrics at Karolinska University Hospital Huddinge
  • Hans-Gustaf Ljunggren*, Professor, CIM, MedH, KI. Innate and adaptive immunity, collaborator in the SARS-CoV-2 project.
  • Jan Albert, Professor. MTC, KI. Expertise: Viral epidemiology and dynamics.
  • Marcus Buggert, PhD, Associate Professor, CIM, KI, Huddinge.  Expertise: world-leading knowledge in cell sorting, gene expression, transcriptional and epigenetic profiling of tissue-resident T cells.
  • Linda Björkhem Bergman, MD, PhD. Clinical collaborator for evaluation for T cell responses in elderly for which we have received a collaborative grant.
  • Kristina Broliden*, Professor and Annelie Tjärnlund*, Associate Prof., KI, Solna. Expertise: In situ immunohistochemistry and fluorescence staining and analysis of tissue sections.
  • Christian Giske, Professor/senior physician, Head of Division of Clinical Microbiology, LABMED, KI. Expertise: Microbiota and antimicrobial resistance.
  • Ujjwal Neogi, PhD, Associate Professor, Division of Clinical Microbiology, LABMED, KI. Expertise: Systems Virology, Immuno-metabolism.
  • Marion Humbert*, PhD, Postdoctoral Fellow, CIM, MedH, KI. COVID project/T cell immunology.
  • Piotr Nowak*, MD, PhD, Adjunct senior lecurer, Team Leader, MedH, KI. Senior Consultant, Karolinska University Hospital, Huddinge. Expertise: Microbiome, Infectious Disease Specialist.
  • Marianne Jansson, Professor. Lund University. Expretise: HIV-1 and HIV-2 host interactions.
  • Erik Melén, Professor of Pediatrics, Department of Clinical Sciences and Education Södersjukhuset, KI. Pediatric allergist, Sachs´ Children’s Hospital. PI of the BAMSE study. 
  • Maria Jenmalm, Professor. Department of Biomedical and Clinical Sciences (BKV), Division of Inflammation and Infection, Linköpings Universitet. Expertise: Clinical immunology in children.
  • Eva Sverremark Ekström, Professor in immunology at the Department of Molecular Biosciences, The Wenner-Gren Institute (MBW), Stockholm University.

Current International Collaborations

  • Alba Grifoni, Researh Assistant Professor. La Jolla Institutet for Immunology, San Diego, USA. Expertise: Viral epitopes and recognition by T cells
  • Ole Lund, Professor, and Morten Nielsen, Professor. Center for Biological Sequence Analysis, Technical University of Denmark, Lyngby, Denmark. Expertise: Cutting-edge bioinformatics to tackle complex virus-host interactions and ability to predict MHC restricted viral epitopes.
  • Emma Hodcroft, postdoc, Institute of Social and Preventive Medicine, University of Bern, and Swiss Institute of Bioinformatics, Lausanne, Switzerland. The core Nextstrain group. Providing sequence information, viral epidemiology, involving current and past spread of endemic human coronaviruses and SARS-CoV-2.
  • Fridtjof Lund-Johansen, PhD, Group leader, Protein Array Group, ImmunoLingo convergence center at University of Oslo. Expertise: Antibody responses.