Zika, dengue fever and West Nile virus: why vaccinations against tropical viruses are complicated

Diseases such as dengue fever and West Nile virus will also become a problem in Germany in the next five to ten years thanks to global warming, predicts researcher Sebastian Ulbert. He has been investigating which vaccines and active ingredients could help us since 2011. In other parts of the world, the dengue virus already has a pandemic-like status. However, vaccination against the virus is complex and not without risk.

Zika, dengue fever or the West Nile virus – all of these tropical diseases are caused by so-called flaviviruses. These pathogens, which are usually carried by mosquitoes, have long been known in many warmer countries. Infections with them are still very rare in Germany, but they are becoming more common.

Sebastian Ulbert researches flaviviruses at the Fraunhofer Institute for Cell Therapy and Immunology (IZI) in Leipzig. He says: "This will also be a very important topic for us in Germany in the future. climate change is responsible for the increase in infections. Increasingly higher temperatures are allowing the mosquitoes that carry the virus to survive further and further north.

This is currently particularly evident in Italy. Ulbert reports: "I was just in northern Italy, in the area around Padua. In the summer of 2022, the intensive care units there were full of people infected with the West Nile virus."

Dengue is not becoming like corona - but mosquito bites are becoming more common

From his point of view, panic is not appropriate, but he assumes that the situation in Germany could be similar in five to ten years' time

, provided that climate change continues to cause higher temperatures. "One consequence, for example, will be that you will no longer be able to sit in your garden and be bitten by a mosquito," predicts Ulbert.

The researcher says that flaviviruses will not reach dimensions similar to those of the coronavirus pandemic. With regard to dengue fibre, however, we can already speak of a pandemic, but it is not happening here. "There have already been severe outbreaks in Brazil and other parts of the world this year. Dengue fever is particularly dangerous for young children, and we are currently seeing many seriously ill people. It is already a serious problem worldwide."

Three pillars against flaviviruses: vaccines, test systems and active substances

There are three important pillars to better protect people against flaviviruses: Vaccines, test systems and active substances that act directly against the viruses when they are already in the body. Sebastian Ulbert and his team have been working on this topic since 2011 and are developing both vaccines and active substances. A vaccine that works is usually the better option, says Ulbert. "Active substances are usually very expensive to produce. This is a problem, especially for diseases that spread quickly and occur in emerging and developing countries."

Administering a vaccine against flaviviruses is not without risk, however. Ulbert explains: "As a rule, you get infected with a virus or are vaccinated and are then immune. With dengue fever, however, there are four different serotypes that circulate. If you have been infected with one of the types or have only been vaccinated against one and then become infected with one of the other three types, you are not only unprotected against this type, but sometimes even more seriously ill."

A vaccination or infection can cause more severe courses

This is due to a phenomenon called "antibody-dependent enhancement of infection", which means that if the body has already developed antibodies against a virus, it attacks a very similar virus with the same antibodies. These bind to the virus, but do not render it harmless because it is different from the originally "trained" virus.

This allows the virus to enter the cells of the immune system, where it can multiply best. "This also makes it more difficult to develop vaccines against other flaviviruses, such as the Zika virus. This could potentially predispose people to a serious infection with the dengue virus, which looks similar."

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In an already authorised dengue vaccine, people are given a mixture of four vaccines that are supposed to be effective against all four serotypes. However, this does not work for everyone. A small proportion of those treated were also found to have a higher risk of severe dengue, says the researcher. "So you need vaccines that are so specific that they only work against a certain type of flavivirus or vaccines that are so comprehensive that you can cover all flaviviruses at once."

Specifically targeted vaccines can minimise the problems

He is currently researching vaccines that ignore certain parts of the so-called E protein (E for "envelope"). This E protein is the same in many flaviviruses. The aim is to ensure that a possible vaccine addresses the virus subtypes and various serotypes with particular precision.

In addition, an active substance against flaviviruses could still play a decisive role. The advantage here is that there are no cross-reactions. The active substances act against all flaviviruses in the same way, similar to how a broad-spectrum antibiotic acts against bacteria. The active ingredient inhibits the viruses in the body.

"The virus hijacks a cell and brings some enzymes with it; it uses other substances from the body cell itself for its reproduction." It is possible to start at this point by attacking the virus enzymes during the reproduction process in the cell. This stops the virus from replicating. "An active substance would be a very good option, especially for people who are already infected with a virus and then come to hospital seriously ill," says Sebastian Ulbert.

There is still a long way to go

before a "super agent" is developed

One of Ulbert's goals would be to develop an active ingredient that works against several viruses at the same time. However, because these differ in their enzyme composition, this is not so easy. We are therefore still a long way from a "super active ingredient" that can eliminate all viruses at once.

The MDR science documentaries "What will the next pandemic be?" and "How can we prevent the next pandemic?" explain which pandemics will threaten humanity in the coming years and what researchers are already doing about them. The second part also provides more insights into the work of Sebastian Ulbert and his team.

Article from "mdr" from 14 November 2023