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Immunology of Viral Hepatitis and Infections in Liver Cirrhosis

Hepatitis viruses A-E pose a major health challenge worldwide. Acute infections with hepatitis B (HBV), C (HCV), D (HDV) or E (HEV) can progress to chronic hepatitis and lead to liver cirrhosis and hepatocellular carcinoma. Chronic viral hepatitis affects more than 350 million people worldwide. While direct-acting antiviral drugs provide a cure for chronic hepatitis C, the long-term effects on the immune system after the infection is cured are not fully understood. While direct-acting antiviral nucleos(t)ide analogues can treat chronic hepatitis B, complete cure is rare. Innovative approaches, particularly modulation of the immune response to HBV, hold promise for a cure. Chronic hepatitis D is always a co-infection with HBV and thus concepts to cure HBV will also target HDV. In chronic hepatitis E, which is unique in immunocompromised patients such as organ transplant patients, enhancing the immune response against HEV may be a novel strategy. In people with cirrhosis of the liver, regardless of the cause, the immune system is compromised and susceptibility to infection is increased. In particular, bacterial infections of the peritoneal cavity due to ascites contribute significantly to disease progression. Our research group focuses on understanding immune responses to hepatitis viruses and developing biomarkers to better stratify patients for new therapeutic strategies to modulate the host immune system in the effort to combat chronic viral hepatitis. In addition, we are exploring the mechanisms underlying immunodeficiency in liver cirrhosis and investigating immunomodulation strategies to improve survival in these vulnerable patients.

Personalised Immunotherapy

Our motivation is to address fundamental questions of human immunology and translate them into personalized therapies and diagnostics. Specifically, our laboratory discovers new applications of antibodies and B cells to treat and prevent human infectious diseases. Effective vaccines against some viruses that escape antibody responses remain elusive. To tackle this challenge, we develop methods to better understand B cell responses, the cells that produce antibodies. We design tailored vaccines and provide novel solutions for infection diagnostics.

Computational Biology for Individualised Medicine

Infections are among the biggest threats to health and the most significant causes of death worldwide. Our aim is to reveal the host genetic risk factors and their downstream molecular pathways, which are crucial to make progress in understanding and treating infectious diseases in an individualised manner as well as to improve the identification of patients at risk. The department of the HZI is part of the developing CiiM and currently housed at the TWINCORE in Hannover. Students and postdocs – We are always looking for bright and enthusiastic students and postdocs (funded by e.g. the ERC starting grant). For more about our projects, please contact us by email.

Individualised Medicine for Viral Infections

Opportunistic infections remain a serious threat to immunocompromised individuals, such as transplant recipients. We study opportunistic herpes viruses, such as the cytomegalovirus (CMV) by developing unique technologies for real-time measurement of virus growth, allowing us rapid identification of antiviral activity of primary samples and virtually any immune cell subset. This allows us to identify at-risk populations and develop targeted antiviral therapies for treatment and prevention of opportunistic viral infections. In the course of the COVID pandemic, our expertise in virus genetics was used to clone pseudoviruses expressing variants of the SARS-CoV-2 spike protein for the assessment of the neutralization capacity of sera or monoclonal antibodies, and this technology is pursued in the identification of correlates of immune protection in vaccinated or convalescent populations. We team with local and international teams of physicians and epidemiologists, providing technical support and scientific advice on complex laboratory serological diagnostics. In March 2019, Prof Dr. Dr. Luka Cicin-Sain was jointly appointed by the MHH (Hannover Medical School) and HZI (Helmholtz Centre for Infection Research) as CIIM Professor for "Individualised Medicine of Viral Infections", and as of 2021 he leads the CiiM-associated Department of “Viral Immunology” (VIRI) at the Helmholtz Centre for Infection Research in Braunschweig.

Infection Biology

Microbial communities consisting of bacteria, fungi and viruses colonize all surfaces of the human body. They are referred to in their entirety as the microbiome. The composition of the microbiome varies between individuals and also within an individual in the course of life. Important influencing factors at the beginning of life are the mode of birth and diet, later the intake of antibiotics and medication as well as long-term diets, the state of health, but also sport and stress play a role. In recent years, a large number of studies have begun to investigate the extent to which the microbiome and its changes actively contribute to our health and the development of diseases. For various diseases, it has been shown in animal models and clinical studies that certain changes in the microbiome influence either the development or the course of e.g. chronic inflammatory bowel diseases or susceptibility to infections. This has led to the development of novel microbiome-based therapies that are currently being investigated in animal models and clinical studies. Prof. Strowig's department uses interdisciplinary approaches from microbiological, immunological and bioinformatic methods to gain a molecular understanding of the complex interactions between the intestinal microbiome and the host. The knowledge that can be gained from this forms an important cornerstone for the development of new individual prevention and therapy approaches. The close cooperation between the MHH and HZI at the CiiM will enable research results from basic research to be transferred more directly into practice in the future. One example is the successful establishment of a microbiome analysis platform, which is essential for researching the influence of the host's microbiome on its susceptibility to infections and has already been used for various patient cohorts (RESIST-SeniorIndividuals, LöwenKIDS). Another example is the identification of specific microbiome components that can be used in preclinical models to prevent colonization with disease-promoting bacteria.

Computational Biology for Infection Research

The group studies microbial communities, including bacteria, viruses and eukaryotic community members, in the context of human health and disease. Direct metagenome, -transcriptome or -proteome sequencing of microbial community samples enables the study of microorganisms that cannot be obtained in pure culture, corresponding to most of the microbial world.

CAIMed Group 1b: AI and Bioinformatics

The identification of genetic risk factors and their molecular signaling pathways as well as the development of predictive models for disease progression and severity are crucial for progress in the understanding and individualized treatment of diseases. At the MHH, existing and planned patient cohorts with state-of-the-art (single-cell) multi-omics data are available. The bioinformatics junior research group will focus on the pre-processing of molecular data in order to create standardized data sets for the analyses of the other CAIMed junior research groups. The aim is to integrate this data on an unprecedented scale using innovative AI methods. These include the identification of factors that correlate with disease severity and progression using causal inference methods. Furthermore, the investigation of cell type-specific genetic effects on molecular characteristics will be carried out using the "deconvolution" method. Finally, mathematical models such as support vector machines will be developed to predict individual reactions to diseases/treatments and thus create a molecular basis for the stratification of patient groups. The aim is to promote the implementation of these mathematical models in medical treatment or diagnostic procedures as a crucial first step towards individualized prevention. Close cooperation with the Integrative Multi-Omics Data group is planned.

Clinical Bioinformatics

Personalized medicine offers a significant opportunity to enhance public health by accounting for individual variability in genes, environment, and lifestyle. The "Clinical Bioinformatics" research group follows this direction, aiming to unravel the intricate molecular mechanisms underlying infection and aging. Through this pursuit, we strive to develop precise, individualized treatment strategies. Our research aims to develop and apply "bioinformatics approaches" to pinpoint the genetic and epigenetic factors influencing infection-induced immune responses by integrating multi-omics data from patients and constructing computational models that predict an individual’s risk of infectious diseases. We interact with experimental collaborators and clinical experts to verify our findings and promote their translation into medical treatments or diagnostic procedures. Our ultimate goal is to contribute to the main research focus of CiiM/MHH: the tailored and improved prevention, diagnosis, and treatment of infectious diseases and cancer for individual patients or patient groups. Within this framework, the team led by Prof. Dr. Cheng-Jian Xu is primarily dedicated to the domains of diagnosis, risk assessment, early detection, and patient stratification.

HZI Podcast: Our immune system competing against diseases

Liver transplantation: Pattern of chronic rejection decoded

Two types of rejection “Chronic and acute rejection differ in terms of cause, progression and treatment,” says first author Dr Bastian Engel, MHH-Clinical Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology (GHIE). “In chronic rejection,…

The CiiM mourns the loss of its founding director Prof. Michael Manns

"With Michael Manns, we have lost the initiator and architect of the CiiM. He pursued the vision of individualized infectious disease medicine with determination and created structures that form the basis of our work today. For me personally, he was a mentor, advisor,…

Comorbidities in HIV: Big data study reveals molecular links

“People with HIV often suffer from non-AIDS-related comorbidities such as cardiovascular disease, liver disease, or cancer. They are more prone to chronic inflammation in the body, which causes them to age faster and have a lower life expectancy than other people,” says…

Groundbreaking for the Centre for Individualised Infection Medicine (CiiM)

"The COVID-19 pandemic has just shown us how important infection research and personalised medicine are - and that research findings need to to be transferred more quickly from bench to bedside," said Lower Saxony's Science Minister Falko Mohrs. “The life sciences are…

CiiM Founders' Award given to Michael Manns

Prof. Dr. Michael Manns took on the role of founding director in 2015, thereby formally launching CiiM. Under his leadership and in close cooperation with the then managing director of the Helmholtz Centre for Infection Research, Prof. Dr. Dirk Heinz, crucial funding…

BCG Vaccine ‘Trains’ Immunity Through Lasting Epigenetic Rewiring

The Bacillus Calmette‑Guérin (BCG) vaccine, in use for nearly a century to protect against tuberculosis, has long intrigued scientists for its ability to confer non‑specific protection against other infections. A new study led by the Centre for Individualised Infection…

Lower Saxony honors the life's work of Professor Michael Manns

‘It is a particular pleasure for me to honour Professor Michael Manns with the Grand Cross of the Order of Merit of Lower Saxony. This is in recognition of an impressive life's work and a sign of our appreciation for an outstanding and highly renowned scientist in our…

Why the flu vaccine is less effective in older people

Every year at the beginning of October, the flu epidemic rolls around. “Because older people in particular have an increased risk of a severe course of the disease, effective vaccines are especially important for them,” says Prof. Yang Li, Scientific Director of the…

Lyme disease: Probability of developing the disease is genetically predisposed

If a tick is infected with the pathogen Borrelia burgdorferi s. l. (sensu lato = in the broader sense), these bacteria can be transmitted to humans through a tick bite and cause illness. Various organ systems can be affected: the skin, the nervous system or the joints.…

‘The star is the team!’

Full support from the state of Lower Saxony After the welcoming remarks by Dean of Research Professor Frank Bengel, Professor Hilfiker-Kleiner and Professor Manns were greeted with thunderous applause. Lower Saxony's Minister of Science Falko Mohrs emphasised that it…

New Research Center for Artificial Intelligence and causal methods in Medicine

The digitalization of the life sciences opens up completely new potential for tackling common diseases such as cancer, cardiovascular diseases, diabetes and neurodegenerative diseases such as Alzheimer's. The Center therefore focuses on linking research data, clinical…

MHH Professor Tobias Welte passed away

Welte was a highly valued partner and colleague to many researchers at the HZI. Particularly close collaborations with Tobias Welte existed, for example, with the HZI "Epidemiology" department under the direction of Prof. Gérard Krause (now WHO) and currently Dr. Berit…

“Aging Clock” reveals aging processes in immune cells

As we age, our immune system also ages. We become more susceptible to infections, vaccinations work less well and the risk of developing immune-related disorders such as autoimmune diseases increases. “In order to better understand how and where exactly the immune…

ERC Proof of Concept Grant for Yang Li

“Prof. Dr. Yang Li impressively combines insights from the life sciences and data science in her research. In doing so, she is laying the foundation for new possibilities for individually adapted diagnoses and therapies in medicine. As head of the Centre for…

What leads to severe COVID-19?

The team was able to identify underlying regulators of the malfunction of the innate immune system in COVID-19 patients and confirm that certain already known genetic risk loci play a role in the development of COVID-19. The results have been published in the journal…

A virus lurking in the connective tissue

As part of the new study, Dr Katarzyna Sitnik, then working in the “Viral Immunology” department at the HZI, headed by Prof Luka Cicin-Sain, and her colleagues naturally infected mice with murine CMV (mCMV). This variant of the virus is used because human CMV (HCMV) is…

Five HZI scientists are “Highly-cited Researchers”

Bioinformatician Prof Alice McHardy uses computational techniques to research the human microbiome as well as viral and bacterial pathogens. She heads the department “Computational Biology for Infection Research” at BRICS (Braunschweig Integrated Center of Systems…

Do women and men react differently to infections?

Hijacking in the immune system

Up to 90% of the world's population carries HCMV. In people with a normal immune system, the infection is usually subclinical, i.e. it does not cause any pronounced symptoms. However, in immunocompromised patients, such as organ transplant recipients, the infection can…

COVID-19 Patientenkohorte hilft bei Aufklärung des Patientenrisikos

Aus der MHH stammen Bioproben und Daten der „ COVID-19-Kohorte “, die seit März 2020 von unterschiedlich stark am Coronavirus SARS-CoV-2 erkrankten Patientinnen und Patienten sowie Kontrollproben von Menschen mit anderen Atemwegserkrankungen aus verschiedenen…

Joint symposium of HZI and McGill University on personalised infection medicine

Personalised infection medicine aims to take into account individual differences in the diagnosis and therapy of infectious diseases. The HZI and McGill University have been building a strategic cooperation on this topic for several years. Clinicians and scientists from…

Who benefits from immunotherapy against hepatitis B?

It is estimated that more than 250 million people worldwide are chronically infected with the hepatitis B virus. Cytotoxic T cells and T helper cells play an important role in fighting viral infections. The constant activation of these immune cells in chronically…

The path to personalised hepatitis D treatment

Hepatitis D is caused by coinfection of hepatitis B patients with the hepatitis D virus (HDV). Up to 20 Million individuals are infected with HDV worldwide including about 250.000 patients in the European Union. There is very limited knowledge on disease pathophysiology…

When the skin aches

It was already known that in both psoriasis and neurodermatitis, T-cells of the immune system migrate from the blood into the skin and drive the inflammation there. Detailed examination of T-cells in blood and skin now led to evidence that in atopic dermatitis they…

How does Long COVID develop? New piece of the puzzle found

After infection with the SARS-CoV-2 virus, up to ten percent of those affected in Germany develop Long COVID. The symptoms associated with it, such as fatigue, concentration problems, respiratory issues, or neurological problems, can last for months or years.…