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Better vaccines against malaria and tuberculosis

The infectious diseases malaria and tuberculosis are responsible for 2.1 million deaths every year. Leiden researchers are currently testing a new tuberculosis vaccine.

The infectious diseases malaria and tuberculosis are responsible for 2.1 million deaths every year. As the vaccines currently available to treat these diseases provide only limited protection, Leiden researchers are working on developing better vaccines. For example, a new tuberculosis vaccine is now being tested in animal trials, and a new malaria vaccine was found to give full protection in animal tests. The first clinical trials will take place in 2017.

100% protection against malaria

Malaria claims more than half a million victims every year, many of whom are children under the age of five. A vaccine to combat this disease has recently become available. ‘That’s excellent news, but this vaccination only offers limited and temporary protection. The reason is that the malaria parasite undergoes several stages of development, all of which look very different, which makes it very difficult for the immune system to recognise the parasite,’  comments Meta Roestenberg, specialist in internal medicine and infectious diseases at the LUMC. The vaccine is based on only one of these stages, which means that a parasite in a different stage can still evade the immune system.

Meta Roestenberg in het lab.
Meta Roestenberg in the lab.

This is one of the reasons that Roestenberg and her colleagues Chris Janse and Shahid Khan at the Parasitology Department are developing a vaccine based on living, attenuated parasites. These parasites have been manipulated by switching off two genes, which means they can no longer cause the illness. Roestenberg: ‘This vaccine gives 100 per cent protection in test animals, so we now intend to test it in humans.’

To allow the development of the vaccine to take place as rapidly as possible, Roestenberg, together with Radboud UMC, will test the vaccine in line with the concept of controlled human infections. This is a clinical test where healthy volunteers are vaccinated and then exposed to the pathogen. The test shows clearly whether or not the volunteers are protected by the vaccine. To test the malaria vaccine, the volunteers are bitten by malaria mosquitoes. Using this method, it is possible to determine very quickly whether or not the vaccine is effective. Based on the results, the decision can then be taken whether to test the vaccine further in Africa. Roestenberg: “We do these kinds of controlled infections not only for malaria but also, for example, for Schistosomiasis and hook worm infections. Even with this fast method of clinical testing, it will unfortunately still take a long time before this vaccine is actually available.”

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Fast vaccine testing with Controlled Human Infections

 

Vaccine with tuberculosis proteins

There is also an urgent need for a better vaccine against tuberculosis. A vaccine is currently available that is used to inoculate children in tropical countries, but it is short lasting and loses its effectiveness in the teenage years. 

Professor Tom Ottenhoff is aiming to develop a vaccine based on several different proteins from the tuberculosis bacterium. His research includes screening the complete genome of the bacteria using blood from people who are immune to tuberculosis and who therefore already have immune cells that fight the bacteria. In a specially devised test, Ottenhoff measures exactly which proteins these immune cells react to. ‘We combine these proteins in a vaccine that we then test on animals to see whether it gives protection. We have already come a long way with this, but it is a huge challenge to make the step to testing on humans,’ Ottenhoff explains. 

Dual vaccine?

To develop the best possible vaccine, it is crucial that the working of the vaccine and the reaction of the immune system can be replicated in a lab environment. Ottenhoff and his colleagues have developed a special test that allows two hundred different immunological proteins to be measured at the same time for how they respond to a virus, bacterium, parasite or foreign protein. The test can be used not only for tuberculosis research, but also for research on other infectious diseases such as malaria. Ottenhoff hopes in the future to work even more intensively with his malaria colleagues. ‘If the new malaria vaccine works well, we could try to add some tuberculosis genes. Maybe it could work as a dual vaccine. But for the time being that’s just speculation.’

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