Over 150 scientists at various locations throughout Germany work together as part of the German Centre for Infection Research (DZIF). The centre focuses on the development of new diagnostic, preventive and therapeutic methods for treating infectious diseases. Scientists from the University and University Hospital of Tübingen and the Max Planck Institute for Developmental Biology are also part of the project. The researchers from Tübingen are mainly involved in research into and the search for new drugs against malaria, gastrointestinal diseases and infections caused by bacteria resistant to commonly used antibiotics. As clinical trials specialists, the researchers from Tübingen have been conducting since November 2014 a clinical trial in Africa for a potential Ebola vaccine on behalf of the World Health Organisation (WHO).
Established in 2012, the German Centre for Infection Research (DZIF) is an affiliation of 32 research institutions at seven sites throughout Germany whose aim is to carry out infection research and develop new diagnostic, preventive and therapeutic methods for treating serious infectious diseases. The centre is divided into central units for use by all members. These units include banks with samples, active agents and pathogens, as well as biocontainment laboratories. The DZIF also has units that are focused on particular themes and bring together researchers from different sites. “The fundamental idea behind the DZIF is to harmonise and structure activities related to infection research in Germany and enable specialists to work together more effectively,” says PD Dr. Benjamin Mordmüller, deputy director of the Institute of Tropical Medicine at Tübingen University Hospital, which is one of the 32 DZIF research institutes. Four African institutes that do research into infectious diseases such as malaria and Ebola in the areas where these diseases are endemic are also affiliated with the DZIF.
The DZIF has formed Thematic Translational Units (TTUs), each of which is dedicated to one specific pathogen or infectious disease. The TTUs bring together experts in basic research, epidemiology and clinical practice in order to achieve the greatest possible synergistic effect and facilitate the transfer of research results as quickly as possible into clinical application.
The TTU “Emerging Infections” pools the activities of ten institutes, including the University Hospital of Tübingen, which are all working on methods to contain Ebola. The TTU “Emerging Infections” is coordinated by researchers from the University of Marburg. At the DZIF’s Tübingen partner site, researchers from the University and University Hospital of Tübingen and the Max Planck Institute for Developmental Biology mainly concentrate on projects relating to malaria, hospital pathogens, infections with antibiotic-resistant bacterial pathogens and of the gastrointestinal tract. Tübingen is the DZIF’s coordinating body for focal projects on malaria and infections caused by antibiotic-resistant bacteria and is also involved in central DZIF areas such as the DZIF Academy, which is specifically focused on the education and training of early career medical doctors and scientists.
At the Institute of Tropical Medicine at the University Hospital of Tübingen, PD Dr. Benjamin Mordmüller heads up the clinical research platform that is part of the DZIF’s TTU “Malaria”, coordinated by Prof. Dr. Peter G. Kremsner, also from the University of Tübingen. The researchers’ aim is to develop new drugs for treating and preventing malaria. “In the African city of Lambaréné, it is perfectly normal for people to contract malaria once or twice a year,” comments the infectious disease researcher. Malaria is still one of the most common infectious diseases and claims hundreds of thousands of lives per year, 90 percent of them in Africa. Young children are at particular risk of contracting the disease and developing complications.
“Malaria is caused by Plasmodium protozoans that are transmitted by female Anopheles mosquitoes, and the disease caused by P. falciparum is the most dangerous form of malaria, with the highest rate of complications,” says Mordmüller. No effective vaccine to prevent infections has yet been brought to market and many parasites have become resistant to commonly used drugs. For Mordmüller the “holy grail of malaria research” is therefore malaria vaccines that can effectively prevent the development of P. falciparum malaria.
With his colleagues in Tübingen and Lambaréné, Mordmüller is working on turning results from cell cultures and infection models into drugs. After thorough testing, the researchers are now working on a clinical infection model that involves the controlled infection of healthy subjects with viable malaria parasites of the type Plasmodium falciparum that are sensitive to all standard anti-malaria drugs without exposing the subjects to health risks. The P. falciparum strain used was produced according to valid pharmaceutical guidelines.
“In our model, all subjects infected with P. falciparum develop malaria. However, we immediately put in place measures to prevent the disease from developing as soon as parasites are detected in the subjects’ blood. Treatment is usually initiated before the very first disease symptoms occur,” says Mordmüller. In the second phase of the trial, the researchers will use the model to test a new vaccine in the form of attenuated malaria parasites aimed at effectively protecting people against the disease. “We have successfully completed the first phase of the trial and we are very hopeful that the vaccine will be effective,” says Mordmüller. If this turns out to be the case, the researchers will drive forward the clinical development of the vaccine for application in Africa.
Researchers from Tübingen University Hospital also participate in research projects in the TTU “Healthcare-associated and Antibiotic-resistant Bacterial Infections”. In Germany alone, hundreds of thousands of patients are infected with so-called hospital bugs, i.e. bacteria that are resistant to several antimicrobial drugs, during a hospital visit. Diseases caused by resistant pathogens have become one of the major healthcare problems, and have increased dramatically over the last ten years. “Many hospital-acquired infections are caused by staphylococci, bacteria that are commonly found in the nose and that are resistant to one or more antibiotics. Hospitalised patients with weakened immune systems are likely to become seriously ill,” says Mordmüller, adding, “it would be a massive step forward if we had a vaccine and more effective drugs for treating such infections.”
The TTU “Healthcare-associated and Antibiotic-resistant Bacterial Infections” coordinated by Prof. Dr. Andreas Peschel therefore specifically focuses on the development of drugs against staphylococci and other antibiotic-resistant bacterial pathogens. He is also involved in what is known as “antibiotic stewardship”, i.e. strategies and programmes to ensure that antibiotics are used correctly, sensibly and specifically, or that their use is limited as much as possible. Clinical trials will be carried out to assess whether the appropriate use of antibiotics and improved infection control measures are able to reduce the burden of antibiotic-resistant bacterial infections.
Researchers from Tübingen University Hospital are also involved in the TTU “Gastrointestinal Infections”, which aims to improve the diagnosis, treatment and prevention of bacterial gastrointestinal infections. Such infections have become rather common: gastrointestinal infections and various forms of diarrhoea kill around five million people globally each year, and approximately half of the world’s population is infected with the gut microbe Helicobacter pylori.
No effective vaccines are available for any of the major gastrointestinal pathogens, and treatment options are largely insufficient. The TTU is therefore working on the development of new selective treatment strategies for specific pathogens or groups of pathogens, rather than using drugs that broadly attack pathogens and commensals alike. Another important research focus is therefore to develop therapies that protect the microbiota during interventions against gastrointestinal pathogens.
In addition to participating in the aforementioned TTUs, clinical trials experts from Tübingen, in cooperation with their partner institute in Lambaréné, are conducting a clinical trial to test the first ever Ebola vaccine (BPSC1001) in Africa on behalf of the WHO. The scientists from Tübingen are in charge of coordinating the trial and also act as sponsor, which means they are responsible for the overall organisation of the trial, from clinical trial insurance to quality control of the Ebola vaccine. “Our partner institute in Lambaréné is in charge of what is by far the most important part of the trial,” says Mordmüller.
“In a phase I clinical trial, the vaccine is given to healthy subjects in order to assess whether it is safe in humans and what kind of immune (antibody) response it evokes. For diseases like Ebola, the goal is to make the vaccine available in the area of the epidemic as soon as possible.” The vaccine candidate has already produced excellent results in animals, meaning that the animals that received the vaccine were protected against infection with the virus. The vaccine is not yet approved for human application. Simultaneously with the researchers from Tübingen, research institutions in the USA, Hamburg and Geneva are also assessing the safety of the newly developed vaccine. It is expected that initial results will be available within the next few weeks or so.
Further information:PD Dr. Benjamin MordmüllerInstitute of Tropical MedicineWilhelmstraße 2772074 TübingenTel.: +49 (0)7071 29-8 2187E-mail: benjamin.mordmueller(at)uni-tuebingen.de