Preventing future pandemics

Almost two decades before the recent pandemic, another coronavirus spread around the world – the SARS pathogen SARS-CoV-1. However, the waves of infection caused by SARS-CoV-1 were less pronounced and not nearly as devastating as the outbreak of the closely related pathogen with the serial number 2, which led to lockdowns all over the world for two years. SARS was followed by swine and bird flu, Ebola, MERS, and Zika. All of these infections, some of which can be fatal or, in the case of Zika, can cause serious malformations in newborn babies, share a common property: they originally crossed from animals to humans. And scarcely had we got over the worst of the coronavirus crisis than monkeypox became a threat. Experts agree that further pandemics will follow, probably in quick succession. It is more and more likely that pathogens, which previously circulated regionally, will spread around the globe with the world becoming increasingly connected. We are in a race against time.

“Pathogens don’t wait until we’re ready. We have to learn as quickly as possible what they’re capable of,” emphasizes Professor Reinhard Straubinger, Dean of the Faculty of Veterinary Medicine. Moreover, we must not neglect infections that do not burst forth in a newsworthy fashion, but which nonetheless pose a grave danger to mankind. Tuberculosis leads the global statistics for lethal infectious diseases. It is triggered by bacteria and can infect people and animals. It is estimated that about one third of the world’s population is infected with this pathogen.

Professor Gerd Sutter, an expert in zoonoses and vaccine research, has developed various vaccines. These include a vaccine against the pathogen that causes the severe lung infection MERS, which is transmitted by dromedary camels and belongs to the family of coronaviruses. Sutter’s Chair of Virology at LMU was previously housed on the old campus of the Faculty of Veterinary Medicine next to the English Garden, as was Straubinger’s Chair of Bacteriology and Mycology. Both chairs have moved into a brand new state-of-the-art building on the campus in Oberschleissheim, which is now being officially opened.

Human and veterinary medicine to be practiced side by side

The new building of the Institute of Infection Medicine and Zoonoses is one of the centerpieces of the expanding research center beyond Munich’s northern municipal boundary. “With the range of topics it accommodates, the institute perfectly complements the research strategy of the Faculty of Veterinary Medicine on the new campus,” says Reinhard Straubinger. “Our activities in the veterinary sphere are shaped by the one-health strategy,” he continues. “Animal and human wellbeing can be viewed as two sides of the same coin.” It is becoming increasingly apparent that there is a “growing focus on intersections between human and veterinary medicine.” The work that will be carried out in the institute’s new building and the research on zoonoses and vector-borne diseases will be paradigmatic in this regard. Straubinger himself studies bacterial pathogens that cause diseases in animals but have the potential to infect humans as well.

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Highest safety standards for research

“It’s a great building with state-of-the-art laboratory equipment,” say Straubinger and Sutter. The basement floor and the two upper storeys comprise laboratories, offices, seminar rooms, and a library. Designed by the architecture office bizer Architekten in Stuttgart, the building has a usable floor space of 2,885 square meters, including the basement floors. Total costs for the project amounted to 73.42 million euros.

Latest research results from virology, bacteriology, and mycology require validation in animal models before they become relevant for clinical use. These crucial research steps will now be performed in the new Microbiology Institute’s animal facility. Here scientists can carry out the experiments necessary in fields such as vaccine research. This combination of special laboratories for handling potentially infectious material and a facility housing animals only exists in about a dozen research centers across Germany.

As such, the safety standards in the complex are of the highest level and are suitably elaborate. The safety installations meet stringent BSL3 standards – as requested in the sector – and go beyond statutory requirements. As a result of these measures, researchers are able to work safely with pathogens such as the coronaviruses that cause SARS, MERS, and COVID-19. The safety zone in the institute on the Campus Oberschleissheim is designed such that neither pathogens nor particles contaminated with them can escape the safety area. All waste and wastewater is collected and sterilized in autoclaves, and all exhaust air is cleaned and sterilized via multiple special filters.

Employees entering and working in the safety zone need to be specially trained and have to be equipped with suitable personal protective clothing. The working areas and the personnel airlock are maintained at negative pressure so that in case of an incident any possibly contaminated air is kept in the containment zone. The technical safety precautions are built with redundancy and are designed to protect the environment against any conceivable incidents. The S3 area is designed as a high-safety containment zone that guarantees smooth workflows for research. The BSL3 facility will be made accessible to other research institutes of LMU as well as to other institutions outside LMU once it has been established within the next few years.

Fight against borreliosis

Veterinarian Straubinger studies pathogens that infect animals but also humans. Some of his projects, for example, target what he dubs “death from the puddle.” He is referring to so-called Leptospira, which are spread by mice and rats. These bacteria survive in the kidneys of rodents and are excreted in their urine. In damp environments, they can sometimes survive for months. Dogs, ruminants, pigs, and other animals absorb the bacteria via mucous membranes or skin lesions upon contact with contaminated water. “Although the infection can be mild, it can also cause acute kidney failure and fatal diseases in some cases,” warns Straubinger.

While working in the United States, Straubinger investigated Lyme borreliosis in dogs and demonstrated how fast the pathogens spread in the canines’ skin after the tick bite. Later, he validated a type of repellents called spot-ons, which can be sprayed onto the skin of dogs. In addition, Straubinger’s research is focused on the Anaplasma genus of bacteria, which are also transmitted by ticks.

Zoonoses are spreading at an ever faster rate

The occurrence of zoonoses is a natural event, emphasizes Sutter, and has always been part of life. However, there are growing indications that such outbreaks are becoming increasingly frequent and that the virus carousel is spinning ever faster. Globalization has led to dramatic growth in global connectivity and travel, increasing the probability that pathogens will spread around the planet.

In addition, humans are encroaching ever further on natural habitats by means of settlements and forest clearings in regions like Africa. This increases by far the probability of contact between humans and animals such as viverrids, fruit bats, birds, and monkeys. These animals act as hosts for zoonotic pathogens – and thus the likelihood that a virus will be transmitted from animals to humans increases as well. And finally, the geographic range of pathogens is shifting as a result of climate change. Some regions of Europe, for example, have long become home to disease-transmitting insects from tropical zones which were previously not found in temperate latitudes.

“Over the past two decades, our technical capabilities in vaccine research against viral infections have rapidly increased,” says Sutter. “This makes it all the more important for us that we’ve got reliable in-house opportunities to test our experimental vaccines in animal models.” In cooperation with the World Health Organization (WHO) and others, Sutter is working on a platform designed to simplify and accelerate the development of vaccines. Up to now, it has taken a decade and more before a vaccine was ready for deployment. In the case of SARS-CoV-2, it was possible to reach the goal sooner only because of massive worldwide efforts.

Sutter uses a classical vaccination virus, an attenuated strain of the vaccinia virus Ankara (MVA), into which specific, harmless components of the respective pathogen are introduced. Upon injection, the so-called vector construct is able to induce an immune response in the vaccinated recipients without posing any risks to their health. His team has already applied the method to build various vaccine candidates, including those against MERS, bird flu, Zika, West Nile fever, and the coronavirus SARS-CoV-2. A vector vaccine constructed on a classical model like this would be easier to manufacture on an industrial scale in global vaccine production, and it is thought to have a longer shelf life than the mRNA-based vaccines that have been widely deployed since the coronavirus pandemic.

A modular concept of the vector vaccine platform might also help to shorten individual development steps, save time in vaccine licensing, and allow for storage of pre-developed vaccines against emerging infections. After all, numerous experiments are required before a vaccine can be administered to humans in clinical trials: in test tubes, in cell cultures, and in animal models as well. Up to now, partner institutes of LMU scientists had to perform the latter just because a suitable facility wasn’t available at LMU. This was leading to avoidable delays and was an obstacle to research at LMU. Once the BSL3 area in Oberschleissheim is fully up and running, research that is in the interest of everyone can be conducted independently and faster than could have been done before. Overall, says Sutter, it is about advancing a series of vaccine projects that will allow scientists to respond faster to outbreaks of potentially dangerous zoonotic pathogens – in a race against time.

Pathogens on the move : MERS, bird flu, Covid-19, monkeypox: infectious diseases are increasingly passing from animals to humans. A feature from the magazine EINSICHTEN