Research group Karin Loré
Few medical inventions have affected and saved so many lives as vaccines against infectious diseases. Our research is focused on understanding how the immune system reacts to vaccination and how different types of vaccines work. We test new vaccines under development as well as evaluate existing licensed vaccines in different patient groups.
Understanding mechanisms of vaccination
Few medical inventions have affected and saved so many lives as vaccines against infectious diseases. The challenges we are facing today with developing effective vaccines to several of the world’s most serious infectious diseases (e.g. HIV-1/AIDS, malaria, tuberculosis), new pandemics as well as designing therapeutic vaccines to tumors and/or allergies require a much more intimate understanding of the mechanisms dictating vaccine responses.
The development of vaccines based on nanoparticles or mRNA encoding for pathogen antigens has emerged as a new era in vaccinology. The potential impact of these new vaccine technologies is enormous both in terms of safety and cost reduction. Yet, a lot of fundamental understanding of the vaccine: host interactions and the immune functions dictating the quality of responses after their administration is largely lacking. Our group has had a long term focus on central questions in vaccinology related to both the early events after vaccine administration and the induction and quality of vaccine antigen-specific immunity. This includes studies of how vaccine antigen, adjuvants and mRNA vaccines interact with different cell populations at the site of injection and further disseminate in the body. Since induction of durable and high titers of antibodies with epitope breadth is a prerequisite to prevent many serious infections, several of our projects address the development of B cell responses from the germinal center reaction in lymph nodes to induction of durable and high titers of antibodies with broad specificity.
With a better understanding of how the immune system interacts with vaccines we would be better positioned to select formulations that can elicit stronger immunity, be used at lower doses or with fewer immunizations and are not associated with side effects.
Ongoing research
In ongoing projects we investigate:
- How the early innate immune functions e.g. cell activation and antigen production after mRNA vaccine delivery influence the quality of the vaccine-specific responses.
- How antigens expressed by mRNA vaccines or on nanoparticles can increase vaccine-specific B cell and T cell immunity.
- Correlates between innate immune profiles and the induction of high-quality and durable antibody responses to licensed vaccines in human cohorts.
- How different novel adjuvants stimulate cell populations and enhance and polarize the immunity to be suitable to different infections or tumors.
Application and development of computational tools for immunological data
High-throughput technologies allow us to understand the immunological system as never seen before. However, as the data dimensionality increases, there is a need for the use of computational tools to explore and analyze these complex datasets. Our laboratory uses whole transcriptomics, deep B cell receptor sequencing, and bead-based protein arrays to decipher how our immune system is triggered upon vaccination. We have used transcriptomics to establish early transcriptional changes after vaccination in different tissues and different vaccine platforms. In addition, we are also studying antibody evolution, by integrating both antigen-specific sequencing and deep sequencing of B cell receptors to study antibody lineage development in vaccine trials. Finally, we are also developing new computational biology tools such as R packages and pipelines to help process and analyze these datasets.
The research group
Karin Lore
Professor/Research group leaderGroup members:
- Rodrigo Arcoverde, PhD student.
- Olivia Engstrand, Research assistant.
- Florian Gegenfurtner, PhD student.
- Fredrika Hellgren, PhD student.
- Klara Lenart, PhD student.
- Marcos Miranda, Visiting researcher.
- Annika Reinhardt, PhD, Research specialist.
- Xianglei Yan, PhD student.
Alumni
- Sebastian Ols, PhD student.
- Alberto Cagigi, Senior lab manager.
- Inga Szurgot, Postdoctoral fellow.
- Elizabeth Thompson, PhD student.
- Ang Lin, PhD student.
- Gustaf Lindgren, PhD student.
- Kerrie Sandgren, Postdoctoral fellow.
- Maria Vono, Postdoctoral fellow.
- Frank Liang, PhD student.
- Will Adams, PhD student.
- Cornelia Gujer, PhD student.
- Emily Bond, PhD student.
Affiliated group member
- Taras Kreslavskiy, Principal researcher.
Team Taras Kreslavskiy.
Cooperations
Antibody responses to RSV nanoparticle vaccines:
- Neil King, Andrew J Borst, David Baker, Institute for Protein Design, University of Washington, Seattle, USA.
- Laurent Perez, University of Lausanne, Lausanne University Hospital, Department of Medicine, Division of Immunology and Allergy and Center for Human Immunology. Lausanne, Switzerland.
- Masaru Kanekiyo, Tracy Ruckwardt, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, USA.
B cell diversity and affinity after vaccination:
- Gunilla Karlsson-Hedestam, Martin Corcoran, Benjamin Murrell, Karolinska Institutet, Department of Microbiology, Tumor and Cell Biology.
- Taras Kreslavskiy, Karolinska Institutet, Department of Medicine Solna.
SARS-CoV-2 mRNA vaccine testing:
- Benjamin Petsch, Kim Schwendt, Edith Jasny, CureVac AG.
SARS-CoV-2 nanoparticle vaccine testing:
- Mimi Guebre-Xabier, Nita Patel, Gregory Glenn, Gale Smith, Novavax, Gaithersburg, USA.
- Galit Alter, Harvard Medical School, the Ragon Institute of MGH, MIT, USA.
Systemic and mucosal immune responses to SARS-CoV-2 infection and vaccination:
- Anna Smed Sörensen, Karolinska Institutet, Department of Medicine Solna.
Immune responses to SARS-CoV-2 vaccination in immunocompromised patients:
- Stephan Mielke, Per Ljungman, Gustaf Lindgren, Anna Nordlander, Andreas Björklund, Department for Cellular Therapy and Allogeneic Stem Cell Transplantation, Karolinska University Hospital Huddinge,
- Hans-Gustaf Ljunggren, Marcus Buggert, Karolinska Institutet, Center for Infectious Medicine, Department of Medicine, Huddinge.
- Soo Aleman, Karolinska Institutet, Department of Medicine, Huddinge.
Innate and adaptive immune responses to SARS-CoV-2 vaccination in naïve and convalescent individuals:
- Clas Ahlm, Mattias Forsell M, Umeå University, Umeå, Sweden.
- Anja Rosdahl, Sara Cajander, Örebro University and Örebro University Hospital, Sweden.
Immunity after SARS-CoV-2 vaccination in patients with chronic kidney failure:
- Anja Rosdahl, Örebro University and Örebro University Hospital, Sweden.
- Helena Hervius Askling, Karolinska Institutet, Department of Medicine Solna and Karolinska University Hospital.
Immunity after intranasal delivery of a live-attenuated pertussis vaccine BPZE-1:
- Marcel Thalen, Iliad Biotechnologies, Belgium.
- Camille Locht, Pasteur Institute, France.
Testing of an agonistic anti-CD40 antibody as adjuvant:
- Ulrich Pessara, Daniel Parera, Stephan Fischer, MAB Discovery, Polling, Germany.
Nanoparticle-based PfCSP malaria vaccine testing:
- Hedda Wardemann, German Cancer Research Center, Heidelberg, Germany.
- Jean-Philippe Julien, The Hospital for Sick Children Research Institute, Toronto, Canada.
- Elena A. Levashina, Vector Biology Unit, Max Planck Institute for Infection Biology, Berlin, Germany.
Next-generation bacterial mRNA Vaccines – BAXERNA 2.0:
- Vlaams Instituut voor Biotechnologie (VIB), Ghent, Belgium.
- Ghent University, Belgium.
- Vrije Universiteit Brussel (VUB), Belgium.
- Institut Pasteur, Paris, France.
- Radboud University Medical Center (UMC), Nijmengen, The Netherlands.
- Université Libre de Bruxelles (ULB), Belgium.
- Vaccine Formulation Institute (VFI), Geneva, Switzerland.
- RheaVita, Ghent, Belgium.
- Quantoom, Nivelles, Belgium.
Advanced vaccine adjuvant development program:
- Vaccine Formulation Institute (VFI), Geneva, Switzerland.
- Neil King, Institute for Protein Design, University of Washington, Seattle, USA.
- Desert King International, San Diego, CA USA.
- VIDO-InterVac, University of Saskatchewan, SK, Canada.
Research support
- The Swedish Research Council.
- The Bill and Melinda Gates Foundation.
- Cancer foundation.
- Knut and Alice Wallenberg foundation/SciLifeLab.
- Karolinska Institutet faculty funds.
- Wallenberg Long term bioinformatics support (WABI).
- Horizon Europe – BAXERNA 2.0
- National Institutes of Health (NIH) – Adjuvant Development Program in Infectious and Immune-Mediated Diseases
Selected publications
Multivalent antigen display on nanoparticle immunogens increases B cell clonotype diversity and neutralization breadth to pneumoviruses.
Ols S, Lenart K, Arcoverde Cerveira R, Miranda MC, Brunette N, Kochmann J, Corcoran M, Skotheim R, Philomin A, Cagigi A, Fiala B, Wrenn S, Marcandalli J, Hellgren F, Thompson EA, Lin A, Gegenfurtner F, Kumar A, Chen M, Phad GE, Graham BS, Perez L, Borst AJ, Karlsson Hedestam GB, Ruckwardt TJ, King NP, Loré K
Immunity 2023 Oct;56(10):2425-2441.e14
Cell targeting and immunostimulatory properties of a novel Fcγ-receptor-independent agonistic anti-CD40 antibody in rhesus macaques.
Yan X, Ols S, Arcoverde Cerveira R, Lenart K, Hellgren F, Ye K, Cagigi A, Buggert M, Nimmerjahn F, Falkesgaard Højen J, Parera D, Pessara U, Fischer S, Loré K
Cell Mol Life Sci 2023 Jun;80(7):189
Unmodified rabies mRNA vaccine elicits high cross-neutralizing antibody titers and diverse B cell memory responses.
Hellgren F, Cagigi A, Arcoverde Cerveira R, Ols S, Kern T, Lin A, Eriksson B, Dodds MG, Jasny E, Schwendt K, Freuling C, Müller T, Corcoran M, Karlsson Hedestam GB, Petsch B, Loré K
Nat Commun 2023 Jun;14(1):3713
A third dose of the unmodified COVID-19 mRNA vaccine CVnCoV enhances quality and quantity of immune responses.
Lenart K, Hellgren F, Ols S, Yan X, Cagigi A, Cerveira RA, Winge I, Hanczak J, Mueller SO, Jasny E, Schwendt K, Rauch S, Petsch B, Loré K
Mol Ther Methods Clin Dev 2022 Dec;27():309-323
Route of Vaccine Administration Alters Antigen Trafficking but Not Innate or Adaptive Immunity.
Ols S, Yang L, Thompson EA, Pushparaj P, Tran K, Liang F, Lin A, Eriksson B, Karlsson Hedestam GB, Wyatt RT, Loré K
Cell Rep 2020 Mar;30(12):3964-3971.e7
Live attenuated pertussis vaccine BPZE1 induces a broad antibody response in humans.
Lin A, Apostolovic D, Jahnmatz M, Liang F, Ols S, Tecleab T, Wu C, van Hage M, Solovay K, Rubin K, Locht C, Thorstensson R, Thalen M, Loré K
J Clin Invest 2020 May;130(5):2332-2346
Monocytes Acquire the Ability to Prime Tissue-Resident T Cells via IL-10-Mediated TGF-β Release.
Thompson EA, Darrah PA, Foulds KE, Hoffer E, Caffrey-Carr A, Norenstedt S, Perbeck L, Seder RA, Kedl RM, Loré K
Cell Rep 2019 Jul;28(5):1127-1135.e4
TLR-adjuvanted nanoparticle vaccines differentially influence the quality and longevity of responses to malaria antigen Pfs25.
Thompson EA, Ols S, Miura K, Rausch K, Narum DL, Spångberg M, Juraska M, Wille-Reece U, Weiner A, Howard RF, Long CA, Duffy PE, Johnston L, O'Neil CP, Loré K
JCI Insight 2018 May;3(10):
Efficient Targeting and Activation of Antigen-Presenting Cells In Vivo after Modified mRNA Vaccine Administration in Rhesus Macaques.
Liang F, Lindgren G, Lin A, Thompson EA, Ols S, Röhss J, John S, Hassett K, Yuzhakov O, Bahl K, Brito LA, Salter H, Ciaramella G, Loré K
Mol Ther 2017 Dec;25(12):2635-2647
Open positions and thesis projects
We are always interested to get in touch with talented potential co-workers. If you are interested in doing research within our group, as a post-doc, PhD student or degree project student, please contact the group leader Karin.lore@ki.se.