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Characterization of pathogen-specific T cells in viral hemorrhagic fever
Summary
Lassa virus (LASV) causes Lassa fever, a serious disease with frequent outbreaks in West Africa and up to 900,000 infections each year. Despite its public health importance, little is known about how the virus affects the human immune system, partly because studying LASV requires high biosafety measures and is difficult to do in affected regions. Evidence suggests that an uncontrolled immune response plays a key role in disease severity, but the specific role of immune cells in human patients is still unclear.
This project studies the immune response of Lassa fever patients treated at a hospital in Nigeria, using advanced tools to analyze and characterize T cells and other immune cells. The goal is to understand how these cells influence the course of the disease and why some people develop more severe symptoms than others. The findings will not only improve our understanding of Lassa fever but also help build research capacity in Africa and prepare for future outbreaks of similar viruses.
Our Work Packages (WP):
WP1: Immunological characterization of antigen-presenting cells in Lassa fever patients – aims to identify which immune cells are infected by LASV and how well they can activate T cells.
WP2: Phenotyping and activity-profiling of LASV-specific T cells – focuses on analyzing how T cells respond to LASV and how their function influences disease severity.
WP3: Comparative immune profiling – links immune cell profiles to clinical data and compares them across diseases to identify signatures unique to severe Lassa fever.
These work packages help us to understand how the immune system responds to Lassa virus infection and how this response influences disease severity and outcome.
Team
Dr. Lisa Oestereich
Principal Investigator
E-mail address:
Phone: +49 40 285380-940
Research Group Oestereich
The Research Group Lassa Virus Immunology is based at the Bernhard Nocht Institute for Tropical Medicine Hamburg.
Project related publications
Olal C, Bodmer BS, Rottstegge M, Escudero-Pérez B, Port JR, Bencsik A, Nelson EV, Heung M, Wurr S, Blake O, Adam E, Oestereich L, Baz-Martínez M, Müller-Guhl J, Gallais Y, Anjuère F, Malliere B, Idoyaga J, Hoenen T, Muñoz-Fontela C. Antibody-Based Antigen Delivery to Dendritic Cells as a Vaccination Strategy Against Ebola Virus Disease. J Infect Dis. 2025 Jan 14:jiae613. doi: 10.1093/infdis/jiae613
Ogbaini-Emovon E, Akpede G, Okogbenin S, …, Oestereich L, Krumkamp R. Virus load kinetics in Lassa fever patients treated with ribavirin: a retrospective cohort study from Southern Nigeria. Open Forum Infect Dis. 2024 Oct 15;11(10):ofae575. doi: 10.1093/ofid/ofae575
Mueller HCS, Erameh C, Gelderblom M, …, Oestereich L, Ramharter M, Okogbenin S, Omansen T. Electroencephalography in emerging viral infections: lessons learned from implementing an EEG unit in a Lassa fever isolation ward in Nigeria. PLoS Negl Trop Dis. 2024 Oct 2;18(10):e0012522. doi: 10.1371/journal.pntd.0012522
Niemetz L, Bodmer BS, Olal C, Escudero-Pérez B, …, Oestereich L, Hoenen T, Muñoz-Fontela C. Ebola virus infection of Flt3-dependent, conventional dendritic cells and antigen cross-presentation leads to high levels of T-cell activation. J Infect Dis. 2024 Sep 25:jiae441. doi: 10.1093/infdis/jiae441
Welch SR, Garrison AR, Bente DA, …, Oestereich L, Vatansever Z, Spengler JR, Papa A. Third International Conference on Crimean-Congo hemorrhagic fever in Thessaloniki, Greece, September 19–21, 2023. Antiviral Res. 2024 Feb 29;105844. doi: 10.1016/j.antiviral.2024.105844
Löw K, Möller R, Stegmann C, …, Oestereich L, Braun A, Kunz S, Gerold G. Luminescent reporter cells enable the identification of broad-spectrum antivirals against emerging viruses. J Med Virol. 2023 Nov;95(11):e29211. doi: 10.1002/jmv.29211
Oestereich L, Müller-Kräuter H, Pallasch E, Strecker T. Passive Transfer of Animal-Derived Polyclonal Hyperimmune Antibodies Provides Protection of Mice from Lethal Lassa Virus Infection. Viruses. 2023 Jun 26;15(7):1436. doi: 10.3390/v15071436
Kayem ND, Okogbenin S, Okoeguale J, …, Oestereich L, Dahal P, Ariana P, Günther S, Horby P. Seroepidemiology of Lassa virus in pregnant women in Southern Nigeria: A prospective hospital-based cohort study. PLoS Negl Trop Dis. 2023 May 22;17(5):e0011354. doi:10.1371/journal.pntd.0011354
Erameh CO, Koch T, Edeawe OI, Oestereich L, …, Günther S, Ramharter M, Akideno PE, Kreuels B. Focussed Assessment with Sonography in acute Lassa Fever (FASLa): Development of a point-of-care protocol and description of common ultrasound findings. J Infect. 2023;87(1):27–33. doi: 10.1016/j.jinf.2023.04.008 2022
Thielebein A, Ighodalo Y, Taju A, …, Oestereich L#, Duraffour S#, Ogbaini-Emovon E#. Virus persistence after recovery from acute Lassa fever in Nigeria: a 2-year interim analysis of a prospective longitudinal cohort study. Lancet Microbe. 2022;3(1):e32–e40. doi: 10.1016/S2666-5247(21)00178-6 2021
Strampe J, Asogun DA, Speranza E, …, Oestereich L, Günther S, Connor JH, Muñoz-Fontela C, Ogbaini-Emovon E. Factors associated with progression to death in patients with Lassa fever in Nigeria: an observational study. Lancet Infect Dis. 2021;21(6):876–886. doi: 10.1016/S1473-3099(20)30737-4 2020
Port JR, Wozniak DM, Oestereich L, …, Günther S, Muñoz-Fontela C. Severe Human Lassa Fever Is Characterized by Nonspecific T-Cell Activation and Lymphocyte Homing to Inflamed Tissues. J Virol. 2020;94(21):e01367-20. doi: 10.1128/JVI.01367-20 2018
Speranza E, Ruibal P, Port JR, …, Oestereich L, Günther S, Muñoz-Fontela C. T-Cell Receptor Diversity and the Control of T-Cell Homeostasis Mark Ebola Virus Disease Survival in Humans. J Infect Dis. 2018;218(suppl_5):S508–S518. doi: 10.1093/infdis/jiy352 2017
Lüdtke A, Ruibal P, Wozniak DM, …, Oestereich L, Muñoz-Fontela C, Günther S. Ebola virus infection kinetics in chimeric mice reveal a key role of T cells as barriers for virus dissemination. Sci Rep. 2017;7:43776. doi: 10.1038/srep43776 2016
Ruibal P#, Oestereich L#, Lüdtke A#, …, Günther S#, Muñoz-Fontela C#. Unique human immune signature of Ebola virus disease in Guinea. Nature. 2016;533:100–104. doi: 10.1038/nature17949
Oestereich L, Lüdtke A, Ruibal P, …, Günther S#, Muñoz-Fontela C#. Chimeric Mice with Competent Hematopoietic Immunity Reproduce Key Features of Severe Lassa Fever. PLoS Pathog. 2016;12:e1005656. doi: 10.1371/journal.ppat.1005656
Lüdtke A#, Ruibal P#, Becker-Ziaja B#, …, Oestereich L, Günther S, Muñoz-Fontela C. Ebola Virus Disease Is Characterized by Poor Activation and Reduced Levels of Circulating CD16+ Monocytes. J Infect Dis. 2016;214:275–280. doi: 10.1093/infdis/jiw260
Oestereich L, Rieger T, Lüdtke A, …, Günther S#, Muñoz-Fontela C#. Efficacy of Favipiravir Alone and in Combination with Ribavirin in Lethal, Immunocompetent Mouse Model of Lassa Fever.
J Infect Dis. 2016;213:934–938. doi: 10.1093/infdis/jiv522
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