Karin Loré Group

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. 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.

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.

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.

Karin Loré, professor, karin.lore@ki.se

Phone: 08-524 876 72

Rodrigo Arcoverde, PhD student, rodrigo.arcoverde@ki.se

Erick Bermúdez Méndez, postdoc, erick.bermudez.mendez@ki.se

Olivia Engstrand, PhD student, olivia.engstrand@ki.se

Florian Gegenfurtner, master student, f.gegenfurtner@tum.de

Fredrika Hellgren, MD, PhD student, fredrika.hellgren@ki.se

Gustav Joas, MD, PhD student, joas.gustav@ki.se

Mariana Marmorato, postdoc, mariana.marmorato@ki.se

Annika Reinhardt, PhD, research specialist, annika.reinhardt@ki.se

Eva Rogelj, master student, eva.rogelj@stud.ki.se

Xianglei Yan, MD, PhD student, xianglei.yan@ki.se

Sebastian Ols, PhD student.

Alberto Cagigi, Senior lab manager.

Inga Szurgot, Postdoctoral fellow.

Ang Lin, PhD student.

Gustaf Lindgren, PhD student.

Elizabeth Thompson, 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.

Klara Lenart, PhD student

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, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet
• Taras Kreslavskiy, Department of Medicine Solna, Karolinska Institutet

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, Department of Medicine Solna, Karolinska Institutet

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, Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet
• Soo Aleman, Department of Medicine Huddinge, Karolinska Institutet

 

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, Department of Medicine Solna, Karolinska Institutet 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

 

Malaria vaccine testing:

• Hedda Wardemann, German Cancer Research Center, Heidelberg, Germany
• Jean-Philippe Julien, The Hospital for Sick Children Research Institute
• 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.

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)

Link to all the publications in PubMed by the Group Leader

Multivalent antigen display on nanoparticle immunogens increases B cell clonotype diversity and neutralization breadth to pneumoviruses. Ols S, Lenart K, Cerveira RA, 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, Hedestam GBK, Ruckwardt TJ, King NP, Loré K. Immunity 2023 Oct 10;56(10):2425-2441.e14. PMID: 37689061.

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, Arcoverde R, Szurgot I, Hanczak J, Carter L, King NP, Jasny E, Schwendt K, Rauch S, Petsch B, Loré K. Molecular Therapy Methods and Clinical Development 2022 Dec 8;27:309-323.

Innate immune mechanisms of mRNA vaccines. Verbeke R, Hogan MJ, Loré K, Pardi, N. Immunity 2022 Nov 8;55(11):1993-2005.

Airway antibodies emerge according to COVID-19 severity and wane rapidly but reappear after SARS-CoV-2 vaccination. Cagigi A, Yu M, Österberg B, Svensson J, Falck-Jones S, Vangeti S, Åhlberg E, Azizmohammadi L, Falck-Jones R, Warnqvist A, Falck-Jones R, Gubisch PC, Ödemis M, Ghafoor F, Eisele M, Lenart K, Bell M, Johansson N, Albert J, Sälde J, Pettie D, Murphy M, Carter L, King NP, Ols S, Normark J, Ahlm C, Forsell M, Färnert A, Loré K* and Smed-Sörensen A*. *Senior authors contributed equally. JCI Insight 2021 Nov 22;6(22):e151463.

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** and Loré K**. *These authors contributed equally. **Senior authors contributed equally. Cell Reports 2020 Mar 24;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 and Loré K. Journal of Clinical Investigation 2020 May 1;130(5):2332-2346.

Monocytes Acquire the Ability to Induce Tissue Resident T Cells Via Autocrine IL-10 Signaling Mediating TGFb Release. Thompson EA, Darrah PA, Foulds KE, Hoffner E, Caffrey-Carr A, Norenstedt S, Perbeck L, Seder RA, Kedl RM, Loré K. Cell Reports 2019 Jul 30;28(5):1127-1135.e4.

Induction of Potent Neutralizing Antibody Responses by a Designed Protein Nanoparticle Vaccine for Respiratory Syncytial Virus. Marcandalli J*, Fiala B*, Ols S, Perotti M, de van der Schueren W, Snijder J, Hodge E, Benhaim M, Ravichandran R, Carter L, Sheffler W, Brunner L, Lawrenz M, Lanzavecchia A, Dubois P, Sallusto F, Lee KK, Veesler D, Correnti C, Stewart LJ, Baker D, Loré K, Perez L**, and King NP**. *First authors contributed equally. **Senior authors contributed equally. Cell. 2019. 176(6):1420-1431.

TLR-adjuvanted nanoparticle vaccines differentially imprint 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 CL, Duffy PE, Johnston L, O’Neil C, Loré K. JCI Insight 2018 May 17;3(10):e120692.

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. Molecular Therapy 2017 Dec 6;25(12):2635-2647.

Vaccine Priming is Restricted to the Draining Lymph Nodes and Controlled by Adjuvant-Mediated Antigen Uptake. Liang F, Lindgren G, Sandgren KJ, Thompson EA, Francica JR, Seubert A, De Gregorio E, Barnett S, O’Hagan DT, Sullivan NJ, Koup RA, Seder RA, Loré K. Science Translational Medicine 2017 Jun 7;9(393):eaal2094.

Neutrophils acquire antigen presentation capacity to memory CD4+ T cells in vitro and ex vivo. Vono M, Lin A, Norrby-Teglund A, Koup RA, Liang F, Loré K. Blood 2017 Apr 6;129(14):1991-2001.