VIVAC research group: Vaccines and Immunotherapies against Viruses And Cancer
Our research is focused on basic research but also on development of vaccines and new immune-therapies against viral diseases and cancer.
The research group has several national and international collaborations with both academia and the pharmaceutical industry. The translational research is conducted at Karolinska Institutet, ANA Futura in Flemingsberg in in collaboration with Karolinska University Hospital Huddinge.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease 2019 (COVID-19). In the majority of cases the infection causes mild to moderate respiratory illness without any need for treatment. However, underlying conditions and higher age are more likely to develop severe disease and death.
The objective of our research is to better understand the immunology of SARS to develop a vaccine that activate a broad humoral and cellular immune response against several SARS-CoVs. The majority of current vaccines on the market target only the spike protein. These vaccines have been shown to be highly effective but may also be sensitive to mutations that may impair neutralizing antibody responses to these vaccines, and may not provide protection against other or new SARS-CoVs. The goal with our vaccine is to activate immune responses against multiple proteins of SARS-CoVs. To achieve this goal we use more than one protein in our vaccine thereby activating a broadly reactive immune response. The vaccine is currently tested in a phase I clinical trial at the Karolinska University Hospital.
Link OPENCORONA: https://ki.se/en/research/opencorona
The OPENCORONA research project in social media:
Viral hepatitis is a major health problem with approximately half a billion people infected world-wide. The viruses that primarily causes liver inflammation are hepatitis A, B, C, D and E. The infection is characterized by mild to severe disease, including jaundice, fever, myalgia, nausea, fatigue, vomiting, fatty liver, cirrhosis, liver failure and liver cancer. Prevention is available by prophylactic vaccines for hepatitis A, B and D, but not for hepatitis C and E. Antiviral treatments are available for hepatitis B, C and D, but with varying responses depending on the type of infecting virus.
The objective of our research is to develop an immune-therapy that neutralize the circulating virus and clear infected cells by activating both neutralizing antibodies and T cells to HBV and HDV and thereby limiting the spread of the infection and eliminating HBV- and HDV-infected cells. We hope to take this approach to clinical testing in the coming years.
Crimean-Congo Hemorrhagic Fever (CCHF)
In this European Union funded project we are developing a vaccine against CCHF virus. The CCHF infection is caused by an RNA virus of the Nairoviridae family. The virus is transmitted by the Hyalomma tick, which exists in parts of Europe, Africa, the Middle East and parts of Asia. Due to global warming, there is a risk of spreading to other parts of the world. The virus is primarily transmitted to people from ticks and livestock animals, contact with blood and other tissue from infected animals and humans. Risk groups include healthcare workers, abattoir workers, and the inhabitants of endemic rural areas. The virus causes severe viral hemorrhagic fever outbreaks, with a case fatality rate of 10–40%.
Our role in this project is to evaluate different vaccines and platforms to develop an effective and safe vaccine against CCHF. We are managing the pre-clinical evaluation of the different vaccine candidates within the project and coordinate the work toward clinical evaluation. We hope that a phase I clinical trial can start in late 2023 or early 2024.
Link CCHF Vaccine: https://www.cchfvaccine.eu
The goal is to develop new immune-therapies against cancer. The main focus is to identify immunological receptors able to recognize mutated antigens expressed by cancer, these receptors can then be engineered to generate CAR-T cells, TCR-T cells and other types of cell therapies. Our group is also developing new methods for manufacturing genetically modified cells for adoptive cell therapy utilizing viral and non-viral genetic engineering approaches.
Research group leader Matti Sällberg
- 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
- Isolation of DNA and RNA
- Agarose gel electrophoresis
- Enzyme Linked Immunosorbant assays (ELISA)
- SDS-PAGE and Western blot
- In vivo imaging (IVIS)
- Viral propagation and neutralization assays (BSL2 and BSL3)
Karolinska Institutet, Swedish Research Council, Swedish Cancer Society, Vinnova (CAMP), Region Stockholm, European Commission (CCHFVaccine, OPENCORONA, ERIHNA, VACCELERATE), Stockholm Life Tech, Center for innovative medicine (CIMED), The Sjöberg Foundation, Ruth and Richard Julin Foundation, Strategic Research Area (SFO) in stem cells and regenerative medicine, and Svenska Läkaresällskapet (SLS).
We actively teach students at several different study programs in the field of biomedical laboratory science, virology, and immunology. We teach at the Study Programme in Biomedical Laboratory Science, Study Programme in Dentistry, Study Programme in Dental Hygiene, Study Programme in Medicine, Study Programme in Nursing Science, and Master´s Programme in Diagnostic Cytology.
Memory profiles distinguish cross-reactive and virus-specific T cell immunity to mpox.
Adamo S, Gao Y, Sekine T, Mily A, Wu J, Storgärd E, Westergren V, Filén F, Treutiger CJ, Sandberg JK, Sällberg M, Bergman P, Llewellyn-Lacey S, Ljunggren HG, Price DA, Ekström AM, Sette A, Grifoni A, Buggert M
Cell Host Microbe 2023 Jun;31(6):928-936.e4
Accelerated DNA vaccine regimen provides protection against Crimean-Congo hemorrhagic fever virus challenge in a macaque model.
Hawman DW, Meade-White K, Leventhal S, Appelberg S, Ahlén G, Nikouyan N, Clancy C, Smith B, Hanley P, Lovaglio J, Mirazimi A, Sällberg M, Feldmann H
Mol Ther 2023 Feb;31(2):387-397
A universal SARS-CoV DNA vaccine inducing highly cross-reactive neutralizing antibodies and T cells.
Appelberg S, Ahlén G, Yan J, Nikouyan N, Weber S, Larsson O, Höglund U, Aleman S, Weber F, Perlhamre E, Apro J, Gidlund EK, Tuvesson O, Salati S, Cadossi M, Tegel H, Hober S, Frelin L, Mirazimi A, Sällberg M
EMBO Mol Med 2022 Oct;14(10):e15821
Novel prime-boost immune-based therapy inhibiting both hepatitis B and D virus infections.
Burm R, Maravelia P, Ahlen G, Ciesek S, Caro Perez N, Pasetto A, Urban S, Van Houtte F, Verhoye L, Wedemeyer H, Johansson M, Frelin L, Sällberg M, Meuleman P
Gut 2023 Jun;72(6):1186-1195
Process Development for Adoptive Cell Therapy in Academia: A Pipeline for Clinical-Scale Manufacturing of Multiple TCR-T Cell Products.
Silva DN, Chrobok M, Rovesti G, Healy K, Wagner AK, Maravelia P, Gatto F, Mazza M, Mazzotti L, Lohmann V, Sällberg Chen M, Sällberg M, Buggert M, Pasetto A
Front Immunol 2022 ;13():896242
A DNA-based vaccine protects against Crimean-Congo haemorrhagic fever virus disease in a Cynomolgus macaque model.
Hawman DW, Ahlén G, Appelberg KS, Meade-White K, Hanley PW, Scott D, Monteil V, Devignot S, Okumura A, Weber F, Feldmann H, Sällberg M, Mirazimi A
Nat Microbiol 2021 02;6(2):187-195
Blocking Entry of Hepatitis B and D Viruses to Hepatocytes as a Novel Immunotherapy for Treating Chronic Infections.
Maravelia P, Frelin L, Ni Y, Caro Pérez N, Ahlén G, Jagya N, Verch G, Verhoye L, Pater L, Johansson M, Pasetto A, Meuleman P, Urban S, Sällberg M
J Infect Dis 2021 Jan;223(1):128-138
The SARS-CoV-2 N Protein Is a Good Component in a Vaccine.
Ahlén G, Frelin L, Nikouyan N, Weber F, Höglund U, Larsson O, Westman M, Tuvesson O, Gidlund EK, Cadossi M, Appelberg S, Mirazimi A, Sällberg M,
J Virol 2020 08;94(18):