Research projects
The IIRVD investigates and develops vaccine strategies for infections with emerging viruses such as Ebola virus and coronaviruses (SARS-CoV-2 and MERS) and other clinically relevant viruses (including HIV, HBV).
In several research projects, we analyze the immune responses induced by vaccines. In particular, we are studying early immune events initiated by the innate arm of the immune system, as well as B- and T-cell responses. We are also investigating sex-specific differences in vaccine responses.
Our research is mainly conducted at the Bernhard Nocht Institute for Tropical Medicine in the Department for Clinical Immunology of Infectious Diseases .
Deciphering adaptive immunity in response to vaccines using immune organoids
In response to epidemic or pandemic outbreaks caused by (re-)emerging viruses such as Ebola virus (EBOV), Middle East respiratory syndrome-related coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), rapid vaccine development is imperative. Currently, the study and characterization of vaccine-induced immunity is largely limited to preclinical animal models and ex vivo analyses of human peripheral blood cells from vaccinated individuals. However, animal models often fail to adequately predict human immune responses. Besides, only a fraction of the immune cells necessary for the development of a long-term immune response are found in the blood. Certain populations such as follicular T helper cells, which play a pivotal role in the activation of germinal center B cells, are found almost exclusively in lymphoid tissue.
This gap can be bridged by using human immune organoid technologies as an in vitro model for investigation of adaptive immune responses to infections and vaccine candidates. We are currently establishing a lymphoid tissue organoid model, using tissue that is removed during clinically necessary tonsillotomies and adenotomies. In general organoids offer the potential to complement in vivo experiments involving animal models, while at the same time providing a more accurate prediction of vaccine responses in humans. Especially with regard to respiratory infections, human tonsils are one of the body’s first line of defense. Therefore, investigation of infection and vaccination effects in organoids derived from this tissue is of particular interest. By stimulation of the immune organoids with vaccine candidates against SARS-CoV2, MERS-CoV and EBOV, we are analyzing underlying mechanisms of differential adaptive immunity to these vaccine candidates.
This project is a collaboration between the Department of Otolaryngology (contact
Anna-Sophie Hoffmann ) and the Leibniz Institute of Virology.
Contact
Valentin Bärreiter , PhD Student
Ilka Grewe , Clinician Scientist
Dissecting Sex Differences in the Immune Response to Vaccines
Vaccines are one of the most impactful public health interventions, preventing millions of infections and deaths worldwide each year. As illustrated by recent epidemic or pandemic outbreaks caused by emerging viruses such as Ebola virus, MERS-CoV and more recently SARS-CoV-2, the need for rapid and strategic vaccine development remains paramount.Men and women differ in their immune responses to vaccination, with women typically developing higher antibody responses but also experiencing more adverse reactions following vaccination than men. However, the exact mechanisms and pathways involved in the differential vaccine outcomes between the sexes remain incompletely understood.
We propose to prospectively investigate and dissect sex-specificity in vaccine immunity against two important emerging respiratory pathogens with pandemic potential and high global significance: MERS-CoV and SARS-CoV-2, two recently discovered novel coronaviruses. A detailed understanding of the molecular factors associated with sex differences in vaccine-induced immune responses may ultimately allow strategic modulation of vaccine immunity and promote individualized vaccine design.
This project is part of the DFG-funded Research Unit 5068 on "Sex differences in immunity".
Contact Tamara Zoran, Scientist
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Evaluation of sex differences in immune responses after immunization against COVID-19
This project evaluates early innate immune responses following immunization with the vaccine candidate MVA-SARS-2-S compared to immunization with an approved mRNA vaccine against COVID-19. At longitudinal time points after each immunization, cytokine levels are analyzed by Luminex, diverse innate cell populations are assessed using flow cytometry, and RNA expression of innate cell subsets are measured using RNASeq. The aim of the project is to evaluate whether there are differences in the vaccine-induced innate immunity between male and female study participants.
This project is funded by the German Center for Infection Research (DZIF)
Contact Anahita Fathi, Clinician Scientist
T cell memory after coronavirus vaccination
Memory T cells are an essential part of the adaptive immune system as they clear infected cells and are necessary for the induction of an efficient humoral response. Therefore, their induction is important to consider during vaccine development. Novel vaccine platforms such as mRNA and viral vectors have been shown to induce strong T cell immune responses, which differ depending on homologous/heterologous prime-boost strategy and time between vaccinations. In this project, we are analyzing the dynamics and function of the T cell response after vaccination with the licensed COVID-19 vaccines and MVA-based vaccine candidates. A better understanding of the post-vaccination T cell response will help to define correlates of vaccine-induced protection, especially against viral variants.
Contact Leonie Mayer, PhD Student
Humoral immunity and B cell memory following vaccination against the human coronaviruses MERS-CoV and SARS-CoV-2
Upon vaccination, naive B cells specific for the vaccine antigen can differentiate into different B cell populations. Plasmablasts and plasma cells secrete high levels of antibodies and are mostly short-lived, whereas memory B cells can survive for years in the absence of the antigen and are important for long-term protection. Binding and neutralizing antibodies are considered important drivers of vaccine-induced protection against infection. In addition, non-neutralizing antibody functions such as antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis (ADCP) are increasingly recognized as an important part of antibody-mediated protection against disease and strongly depend on antibody subclasses.
Here, we analyze longitudinal (memory) B cell dynamics as well as antibody subclasses and functionality. A comprehensive analysis of vaccine-induced B cells and antibodies is important to characterize the magnitude and quality of vaccine-induced immunity and to better understand the impact of different vaccine platforms and schedules on the quality and persistence of immune responses.
Contact Marie Weskamm, Scientists