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Current Projects

Research on vaccine development and therapeutic approaches against COVID-19

The COVID-19 pandemic caused by SARS-CoV-2 requires differentiated research approaches to develop therapeutic methods and vaccines. For this purpose, MVA-based vaccine candidates will be tested in different animal models. The aim is to find a suitable animal model and thus determine the protective effect and efficiency of a vaccine in order to evaluate effective strategies for clinical trials in humans.

MVA-based vaccine candidates in the hamster model

Vaccine development against COVID-19 is highly important, however it requires some pre-clinical experiments before studies in humans can be applied. MVA-SARS-CoV-2 vaccines will be tested for safety and immunogenicity in animal models. The hamster model will be the main focus here, since hamsters express a similarly structured ACE-2 protein and have already been proven as a good animal model in SARS-CoV-1 Research.

Epidemiology and prevention of West Nile virus infection in Germany

West Nile virus (WNV) is a zoonosis that is widespread in all regions of the world and is transmitted to wild birds by various mosquito species. However, it can also spread to humans and horses, whereby, in addition to mostly asymptomatic courses, flu-like symptoms ("West Nile fever") occur in about 20-30% cases and 1-2% even develop of a severe, neuroinvasive form with a mostly fatal outcome.

 

In 2018, West Nile virus was diagnosed for the first time in humans in Germany and was later confirmed as the cause of disease in 5 individuals in 2019. In contrast to the application in horses, there is still no vaccination approved for humans, which is why this development is of high importance. For this, comparative characterizations of immune responses following WNV vaccination and WNV infection in horses will provide a better understanding. This includes qualitative characterization of WNV specific antibody responses as well as T cell activation. In addition, potential vaccine failures will be identified, as well as cross-reactions with other flaviviruses, such as TBE, will be investigated to optimize the development of WNV vaccine candidates for the usage in humans.

 

An improved assessment of the efficacy of WNV vaccination in horses and a better understanding of WNV pathogenesis in animals and humans will be the aim for the development of new therapeutic and preventive strategies.

 

Hepatic tolerance in chronic equine hepacivirus infection

Approximately 3% of the world population is chronically infected with hepatitis C virus (HCV), which causes acute and chronic liver diseases. Since a robust immunocompetent animal model for the development of prophylactic or therapeutic vaccines has not yet been found and the origin of HCV is elusive, the virus most closely related to HCV, equine hepacivirus (EqHV) in horses, is coming more into focus. An improved understanding of this virus is also of great importance to equine medicine, as it has been shown that EqHV can also cause acute and chronic infections.

 

The reason for this expression may be a lack of hepatic tolerance, which prevents permanently infected horses from establishing robust cellular immunity. Therefore, increased knowledge of the mechanisms of hepatic tolerance would help to counteract chronic infections. Therapeutic vaccination is expected to provide an answer to this, by using MVA-based vector vaccine technology. Here, MVA (modified vaccinia virus Ankara) expresses selected EqHV antigens, which are then comparatively analyzed in vaccinations to find those antigens that induce a balanced cellular and humoral antiviral immune response.

 

The aim is to investigate the immune response against EqHV in chronically infected horses and the immunological effects of therapeutic vaccination against EqHV in healthy animals. In addition, this project also represents a potential benefit for human medicine and provides further clues to the origin of HCV.

Evaluation of MVA MERS S immunogenicity and protective efficacy in dromedary camels

MERS-CoV (Middle East Respiratory Syndrome Coronavirus) is the cause of a severe and often fatal respiratory disease in humans. Since the virus naturally circulates in the dromedary, which is a very important livestock with close contact to humans, especially in the Arabian Peninsula, the virus poses a major challenge as a zoonotic pathogen. Dromedaries excrete the virus in large quantities, thus transmission to humans is very productive, whereas human-to-human transmission is less epidemiologically significant.

Accordingly, to interrupt such a chain of infection and to protect humans from infection, it is important to prevent virus excretion from the natural virus reservoir and thus from the dromedary. The most promising method seems to be the effective vaccination of the dromedary as a natural virus host.

The vaccine to be investigated is MVA-MERS-S. The replication-deficient vector virus MVA (Modified Vaccinia Virus Ankara) expresses the MERS CoV S protein and thus is expected to lead to immunity of the dromedary against MERS CoV.

 

The aim of the project is to test the immunogenicity and protective efficacy of the vaccine in the dromedary. The most effective route of vaccine administration, the level and longevity of immune responses (including T cells) induced by vaccination, and the ability of the vaccine to prevent virus shedding will be investigated.

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Bianca Beyersdorf
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