Infection & Immunity
The "Infection & Immunity" work group concentrates on dissecting the host response to infection and vaccination during human cohort studies with primary focus on SARS-CoV2 infection, the Human Immunodeficiency Virus (HIV), oncogenic Human Papilloma Viruses (HPV), Mycobacterium tuberculosis (MTB) and helminth infections (together with AG Inge Kroidl). This includes the molecular characterization of the infecting pathogen, identification of correlates of immune protection from infection and disease progression, biomarker discovery for TB diagnostics and treatment monitoring, characterization of HIV reservoirs, as well as mapping of B cell epitopes upon vaccination. Besides the analysis of systemic cellular and humoral immune responses, the group has proficiency in the analysis of effector cell subsets in human tissue samples using multiplex fluorescence immunohistochemistry combined with detection of viral nucleic acids using in situ hybridization to study the micro-environment of virus-infected cells. The capacity for bioinformatic analysis of large-scale RNA sequencing data and microscopy images is undergoing further development.
The working group is closely affiliated with the International Clinical Trials Unit of the German Center for Infection Research (DZIF) and contributes to human subject specimen processing and biobanking during large international clinical trials and observational studies. The group collaborates closely with the NIMR-Mbeya Medical Research Center in Mbeya, Tanzania and the Instituto Nacional da Saude in Maputo, Mozambique as well as other African Research Centers to support improving the capacity for infectious disease research in endemic settings on the African continent.
Immunology laboratory and work areas
In addition, we offer GCP-compliant laboratory services for partners from the biomedical industry during clinical phase 1 to phase 3 of vaccine studies. This includes the management of investigational medicinal products, the processing of human samples, biobanking and international sample logistics. This includes the processing of blood samples (plasma, serum, isolation of peripheral blood mononuclear cells). The group also has extensive experience in supporting large international clinical trials with a particular focus on Africa. We therefore offer support in sample and reagent logistics, capacity building and the analysis process in various national and international studies. Please contact us for further information.
Analysis of diagnostic RNA signatures by means of microfluidics-based quantitative PCR
Immunomonitoring laboratory
Phenotyping of pathogen-specific T cells on the flow cytometer
Bioinformatic analysis of multi-omics data
Nadia Sitoe, PhD 2023, thesis title: "Inflammatory and prognostic biomarkers associated with pulmonary tuberculosis long-term sequelae after TB treatment in relation to HIV status and lung impairment"
Wilbert Mbuya, PhD 2022, title of the thesis: "Dissecting the Influence of Human Immunodeficiency Virus Type 1 on Human Papilloma Virus Infection, Disease and Immunity"
Caleb Mufong, Gambia, PhD 2022, Title of the thesis: "Defining The Inflammatory Pathway And Prognostic Neutrophil-derived Biomarkers Associated With Pulmonary Morbidity And Long-Term Outcome Of Patients Following TB Therapy"
Astrid Hielscher, Germany, PhD 2020, title of the thesis: "Phylogenetic comparison of plasma- and cell subset derived viral sequences to identify the cellular origin of HIV plasma viremia"
Mohamed Ahmed from Egypt, PhD degree 2019, thesis title: "Exploring sputum independent host biomarkers for detection of Tuberculosis disease and monitoring treatment"
Rebecca Loose, Germany, Bachelor's degree 2017, thesis title: "Assessing novel Bioinformatic approaches for analyses of polychromatic flow cytometry data"
Krutarth Patel, Germany, PhD degree 2017, thesis title: "Development and evaluation of a urine based rapid molecular diagnostic test for pulmonary tuberculosis with potential for point of care: Cape Town cohort"
Mohamed Ahmed from Egypt, Master's degree 2015, thesis title: "Dissecting the dynamics of the Envelope-specific IgG response over the course of HIV infection"
Mkunde Chachage from Tanzania, PhD degree 2013, thesis title: "Immune system modulation by Infections with Helminths and HIV-1: Impact on pathogen-specific T cell responses, regulatory T cells and systemic Immune activation"
Francesco Nicoli from Italy, PhD degree 2013, title of the thesis: "Immunogenicity and immunomodulatory properties of the HIV-1 Tat protein"
Ivy Gloria Mensah from Ghana, PhD student from 2010 to 2014. Graduated September 2014. Thesis title: "Biomarkers for disease progression and treatment; immunological profiles in individuals infected by different species of the Mycobacterium tuberculosis complex in Ghana"
Leigh-Anne Eller from USA, PhD degree 2014, thesis title: "Acute HIV infection in non-subtype B populations: Viral dynamics, laboratory staging and early detection"
Myrna Benninghoff, Germany, PhD degree 2015, thesis title: "Establishment and validation of a molecular worm diagnostic method at the NIMR-MMRC laboratory in Mbeya, Tanzania: Importance of real-time PCR in the diagnosis of worm diseases - evaluation and outlook"
Felicien Moukambi from Gabon, Master's degree 2012, thesis title: "Development and Optimization of a flow cytometry based (TAM-IGRA) method to study phenotypic and functional changes on Mycobacterium tuberculosis-specific T cells in order to identify potential diagnostic markers to discriminate active and latent Tuberculosis"
Research technology platforms and laboratory services
The laboratory is equipped with a 13-colour Beckmann Coulter CytoFLEX Flow Cytometer and has vast experience in the flow cytometric analysis of human cells. This includes characterisation of pathogen-specific T cells after in vitro restimulation or by HLA tetramer staining as well as any other cell type in the blood. The laboratory uses the Flow Cytometry core unit CyTUM-MIH for flow cytometric cell sorting at biosafety S2 and S3 level to allow for downstream analyses of DNA and RNA in sorted cells.
The laboratory serves as a core peptide array laboratory for the European HIV Vaccine Alliance. We use a fully validated peptide microarray assay to map and analyse specific antigenic regions recognized by antibodies elicited by vaccination. The technology is established for both, clinical and preclinical specimen. The technology allows reactivity testing against up to 8000 different peptides in triplicates in multiple samples simultaneously. Custom design of the peptide microarray is performed in collaboration with Dr. Georgios Pollakis (University of Liverpool). Bioinformatic downstream analysis of generated data is well established and can be adapted depending on the research question.
Transcriptome analysis is well established within the lab, with bioinformatic workflows developed in house. A particular focus of our research includes the analysis of low abundant cell populations for the discovery of novel biomarkers. We have expertise in high-throughput analysis of whole blood collected in clinical trials and observational studies as well as in low-input RNA sequencing of sorted rare cell populations such as pathogen-specific T cells.
The laboratory is equipped to provide laboratory services for human sample processing and analysis for clinical studies in Munich and elsewhere. This includes the processing of blood samples (Plasma, Serum, Isolation of Peripheral Blood Mononuclear Cells). The group also has tremendous experience in supporting large international clinical with a specific emphasis on Africa. We therefore provide support on sample and reagent logistics, capacity development and the analytic process in multiple national and international study set ups. Please contact us for more information.
Projects (selection)
- KoCo19-Airway Study
- Long-term follow-up of the cellular and humoral immune response after SARS-CoV-2 infection
- The 2H study: Influence of HIV and treatment with ART on HPV-specific infection, disease and immunity
- iCTU - HIV
- TTU-HIV: Immune control of HIV-1
- TB-personalized medicine
- RaPaed - WP4 TB Novel Diagnostics in children
- African Cohort Study (AFRICOS), see press release: A look inside: Blood-based biomarkers could facilitate the early detection of incipient tuberculosis in people with HIV, LMU Klinikum, 13.07.2022
- ERASE TB - WP3 TB Novel Diagnostics
- DZIF Maternity Leave Stipend - Transcriptomic profiling of MTB-specific T cells to identify novel biomarkers for Tuberculosis disease progression and outcome
- DZIF Application for investment goods
- DFG Systems Epidemiological analysis of the COVID-19 PANdemic accounting for host-virus interaction and human behavior (SEPAN)
The group is closely linked to the international Clinical Trials Unit of the German Center for Infection Research (DZIF) and contributes to sample processing and biobanking for large international clinical trials and observational studies. The group works closely with the NIMR-Mbeya Medical Research Center in Mbeya, Tanzania, and the Instituto Nacional de Saúde in Maputo, Mozambique, as well as with other African research centers to improve the capacity for infectious disease research in endemic areas on the African continent.
Most important funding organizations: DZIF, DFG, EU Horizon 2020, EDCTP