VIVAC research group: Vaccines and Immunotherapies against Viruses And Cancer – Matti Sällberg

Our research is focused on basic research but also on development of vaccines and new immune-therapies against viral diseases and cancer.

Group photo of VIVAC research group: Vaccines and Immunotherapies against Viruses And Cancer.

The research group collaborates nationally and internationally with academic institutions and the pharmaceutical industry. Our translational research is conducted at Karolinska Institutet, ANA Futura in Flemingsberg, in close collaboration with Karolinska University Hospital in Huddinge.

Our research

Viral hepatitis

Viral hepatitis remains a major global health challenge, with approximately half a billion people infected worldwide. The primary viruses responsible for liver inflammation are hepatitis A, B, C, D, and E. These infections can range from mild to severe and are associated with symptoms such as jaundice, fever, myalgia, nausea, fatigue, vomiting, fatty liver, cirrhosis, liver failure, and liver cancer.

Prophylactic vaccines are available for hepatitis A, B, and D, but not for hepatitis C and E. Antiviral treatments exist for hepatitis B, C, and D, though their effectiveness varies depending on the specific virus.

Our research aims to develop an immunotherapy that both neutralizes circulating virus particles and eliminates infected cells by activating virus-specific neutralizing antibodies and T cells targeting HBV and HDV. This dual approach is designed to limit viral spread and clear HBV- and HDV-infected cells. We hope to advance this strategy to clinical testing in the near future.

Crimean-Congo Hemorrhagic Fever (CCHF)

In two European Union-funded projects, we are developing vaccines against Crimean-Congo Hemorrhagic Fever (CCHF). CCHF is caused by an RNA virus belonging to the Nairoviridae family and is transmitted primarily by Hyalomma ticks, which are found in parts of Europe, Africa, the Middle East, and Asia. Due to climate change, there is an increasing risk of the virus spreading to new regions. Transmission to humans occurs through tick bites, contact with infected livestock, or exposure to blood and tissues from infected animals or individuals. High-risk groups include healthcare workers, abattoir staff, and residents of endemic rural areas. The virus causes severe hemorrhagic fever outbreaks, with a case fatality rate ranging from 10% to 40%.

Our role in these projects is to evaluate various vaccine candidates and platforms to develop a safe and effective vaccine against CCHF. We are responsible for the preclinical evaluation of these candidates and coordinating efforts toward clinical testing. Currently, we are conducting a Phase I clinical trial in healthy volunteers to assess the safety and immunogenicity of a DNA-based vaccine delivered by in vivo electroporation. The study began in November 2024 and is expected to be completed during 2025.

Link CCHF Vaccine: https://www.cchfvaccine.eu

Link CCHF VACIM:  https://www.cchfvacim.eu

SARS-CoV-2

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19). In most cases, the infection leads to mild to moderate respiratory symptoms that do not require medical intervention. However, individuals with underlying health conditions and older adults are at greater risk of developing severe illness and experiencing fatal outcomes.

The aim of our research is to deepen our understanding of SARS-CoV immunology in order to develop a vaccine that elicits a broad humoral and cellular immune response against multiple SARS-related coronaviruses. Most current vaccines target only the spike (S) protein, which has proven highly effective but is vulnerable to mutations that may reduce neutralizing antibody responses and limit cross-protection against emerging SARS-CoVs.

Our vaccine strategy involves targeting multiple viral proteins to stimulate a more broadly reactive immune response. By incorporating more than one antigen, we aim to enhance both antibody and T cell responses, thereby improving protection against current and future SARS-related coronaviruses.

Link OPENCORONA: https://ki.se/en/research/opencorona

Immuno-therapies

Our aim is to develop next-generation immunotherapies that harness the body's own immune system to fight cancer. A central focus is the identification of T cell receptors (TCRs) and other immunological receptors that can specifically recognize neoantigens - mutated peptides uniquely expressed by tumor cells. Once identified, these receptors are used to engineer therapeutic immune cells, including TCR-T cells, and other cell-based therapies, enabling precise and personalized cancer treatment. We are also innovating in the area of cell manufacturing, developing new platforms to efficiently generate genetically modified immune cells. These include both viral and non-viral engineering strategies, optimized for safety, scalability, and regulatory compliance. In addition, our group explores factors that influence therapeutic efficacy in the tumor microenvironment, such as hypoxia and immune evasion mechanisms, with the goal of designing therapies that are more resilient in hostile tumor conditions. Our translational efforts bridge basic discovery, preclinical validation, and clinical pipeline development.

Publications

Selected publications

Funding

Grants

  • Swedish Research Council
    1 December 2022 - 30 November 2027
    The proposed doctoral program in advanced therapies (DPAT) focuses on preclinical development and clinical adoption of advanced therapy medicinal products (ATMP), a new class of drugs based on cells, genes or engineered tissues with great potential to effectively treat, or cure, a wide range of diseases. Today, patient access to ATMPs is limited by a lack of personnel with the knowledge of the field needed for these drugs to become routine clinical practice. A coordinated effort to ensure education of health care professionals is needed.DPAT targets teachers within programs relevant to the topic
    medicine and dentistry, nursing, pharmacy and biomedical analyst education. The curriculum builds on the core doctoral training programs, complemented by newly co-developed courses and education activities about the ATMP development chain from research, via translation to implementation in health care, including manufacturing, quality control, regulatory and legal aspects, health economics, ethics, and entrepreneurship.DPAT is a national initiative by five Swedish universities, coordinated by Lund University. The universities contribute with their areas of strength and excellent research milieus within ATMP, as well as collaboration with internationally leading institutions in Europe and the US.By educating the teachers and connecting them closer to research, the doctoral program will significantly strengthen Sweden’s competence in this important field of tomorrows Health Care.
  • Genetic Vaccines and Immune-Based Therapies to Prevent Cancer Caused by Chronic Hepatitis B Virus and Hepatitis D Virus Infections: New Therapies and Models
    Swedish Cancer Society
    1 January 2018
    Chronic infections caused by hepatitis B virus (HBV) and hepatitis D virus (HDV) are a leading cause of liver cancer. For chronic HBV, there is currently a lifelong treatment that suppresses the viral proliferation but does not penalize the infection. For HDV, there is only 24 months of interferon treatment which only cures about 25%. Thus, there is a great need for new treatments for HBV and HDV. We intend to develop new immunological treatments for these infections. We are working on developing a treating vaccine against chronic HBV and HDV infection. This is supposed to be an addition to today's treatment. We start with a combination vaccine against HBV and HDV as a treatment for chronic HBV infection. In the studies that have begun, we have been able to show that the vaccine activates a T cell response to HBV and HDV as well as antibodies that prevent HBV / HDV from infecting new cells, so-called neutralizing antibodies. We intend to identify the best of 10 different vaccine candidates that are then developed for clinical trials in humans. In parallel with this, we also develop more experimental treatment principles. We hope that our research will lead to the treatment of chronic HBV and HDV infections being improved so that we can reduce the risk of developing cancer and serious liver damage. We believe that the vaccine we develop can give the infected control over the infection by reducing the number of cells that are infected and knocking out the cells already infected. If we succeed, this can lead to reduced suffering and reduced healthcare costs.
  • Genetic Vaccines and Immune-Based Therapies to Prevent Cancer Caused by Chronic Hepatitis B Virus and Hepatitis D Virus Infections: New Therapies and Models
    Swedish Cancer Society
    1 January 2017
    Chronic infections caused by hepatitis B virus (HBV) and hepatitis D virus (HDV) are a leading cause of liver cancer. For chronic HBV, there is currently a lifelong treatment that suppresses the viral proliferation but does not penalize the infection. For HDV, there is only 24 months of interferon treatment which only cures about 25%. Thus, there is a great need for new treatments for HBV and HDV. We intend to develop new immunological treatments for these infections. We are working on developing a treating vaccine against chronic HBV and HDV infection. This is supposed to be an addition to today's treatment. We start with a combination vaccine against HBV and HDV as a treatment for chronic HBV infection. In the studies that have begun, we have been able to show that the vaccine activates a T cell response to HBV and HDV as well as antibodies that prevent HBV / HDV from infecting new cells, so-called neutralizing antibodies. We intend to identify the best of 10 different vaccine candidates that are then developed for clinical trials in humans. In parallel with this, we also develop more experimental treatment principles. We hope that our research will lead to the treatment of chronic HBV and HDV infections being improved so that we can reduce the risk of developing cancer and serious liver damage. We believe that the vaccine we develop can give the infected control over the infection by reducing the number of cells that are infected and knocking out the cells already infected. If we succeed, this can lead to reduced suffering and reduced healthcare costs.
  • Vaccine and immunotherapies to prevent liver cancer caused by hepatitis B and D virus
    Swedish Cancer Society
    1 January 2015
    Co-infections in the liver caused by hepatitis B and D virus (HBV / HDV) often have a serious course. HDV can only multiply in liver cells that are already infected with HBV. HBV today requires lifelong treatment, but against HDV there is no good treatment. Thus, there is a great need to develop new treatments for HBV and HDV. This project focuses on developing new treatments for HBV and HDV. We have previously developed this type of treatment for hepatitis C and therefore believe that we have very good conditions for doing this also against HBV and HDV. We will produce so-called genetic vaccines, and gene therapy, to produce T cells that selectively recognize and kill liver cells infected with HBV or HDV. This makes HBV infected that they can hopefully end their lifelong treatment with antivirals as the body's own immune system controls viruses. For HDV, we hope that the infection will heal completely, or prevent it from occurring. To be able to do this in a safe and good way, attempts must be made in mouse models. We will develop a new mouse model that is more similar to human as the mouse will have human liver cells. We hope, of course, that we will be able to develop effective treatments for HBV and HDV to reduce, or even eliminate, the risk of liver cancer caused by these viruses. There are studies showing that both HBV and HDV can be controlled with a good T cell response. Thus, our goal is to be able to treat patients with chronic HBV and / or HDV in a rather near future with antigen activation of T cells with vaccine, or redirection of T cells via gene therapy. Our treating vaccine against HBV is today close to clinic testing. We think we can soon be in the same position for HDV.

Staff and contact

Group leader

All members of the group

Research techniques

  • Genetic engineering
  • Cell culture
  • Enzyme-linked immunosorbent spot (ELISpot) and FluoroSpot assay
  • Fluorescence-activated cell sorting (FACS) analysis
  • Intracellular cytokine staining (ICS)
  • Pentamer/Dextramer staining
  • Proliferation assay
  • Cytotoxicity assay
  • Cloning
  • RT-PCR/PCR
  • Sequencing
  • Isolation of DNA and RNA
  • Agarose gel electrophoresis
  • Enzyme Linked Immunosorbant assays (ELISA)
  • SDS-PAGE and Western blot
  • In vivo imaging (IVIS)
  • Histology
  • Fermentation
  • Viral propagation and neutralization assays (BSL2 and BSL3)

Teaching assignments

We actively teach students at several different study programs in the field of biomedical laboratory science, virology, and immunology. 

We teach at the following study programmes: 

  • Study Programme in Biomedical Laboratory Science.
  • Study Programme in Dentistry.
  • Study Programme in Dental Hygiene, 
  • Study Programme in Medicine, 
  • Study Programme in Nursing Science.
  • Master´s Programme in Diagnostic Cytology.