Before travelling to India to visit an old university friend, Dr. Dirk Linke from the Max Planck Institute for Developmental Biology (MPI) made sure he was fully informed about the precautions he needed to take during his trip – especially with regard to health. Besides the traditional tetanus and polio vaccinations, he was also offered a cholera vaccination, which he decided against. He believed that the risk of contracting cholera, a gastroenteritis that is often fatal, was too low to warrant a vaccination.

"During my holidays in India, I suffered from severe diarrhoea and I was angry with myself for having refused the vaccination," said Linke. In the end, it turned out that he had not contracted cholera, but while he was sick in bed for three days he recalled what the tropical disease specialist had said to him during their conversation: The cholera vaccine is to some extent also effective against enterotoxin-producing Escherichia coli strains (ETEC), which are some of the many pathogens that lead to acute travel diarrhoea.

The reason for this immunological cross-reaction is the structural relationship of the cholera toxin with one of the ETEC toxins. "The fact that the cholera vaccine has such a broad spectrum of activity is just a fortunate coincidence," said Linke adding, "with currently used methods it is impossible to specifically develop such a broad spectrum." However, Linke started to think about such a possibility and he eventually came up with a completely new idea. "We have turned practice on its head. Instead of waiting for experiments to produce suitable recognition molecules, we are now focusing on the surface structures that related bacteria theoretically have in common," said Linke suggesting that this will create the necessary basis for developing a vaccine with a wide-ranging effect.

Linke plans to use bioinformatic methods to identify all the sequences in the genome of various gram-negative pathogens that code for potential surface antigens. “We will then use those with the greatest similarity in as many as possible pathogens,” said the scientist. In a second step, he plans to test experimentally whether the target molecules, which will be selected on the basis of theoretical predictions, are actually produced by the bacteria. “The fact that their sequence is present in the genome of the pathogens does not necessarily mean that they play a role in the infection process,” said Linke. But this is necessary in order for the immune system to recognise the antigen after vaccination.

The interdisciplinary orientation of the MPI, where Linke has been employed for more than five years, has turned out to be a big advantage for the planned work. The Department of Protein Evolution, of which Linke’s group is part, has excellent know-how in the fields of bioinformatics and biochemistry. “This puts us in the excellent position of being able to test our theoretical analyses directly in experiments,” said Linke. “This is very fertile for both sides. The structure at the MPI is rather unique.” The scientist also benefits from experience gained in his other projects which focus mainly on the investigation of bacterial adhesins that enable bacteria to adhere to the intestinal mucosa of the host, for example. “Although the development of the vaccine is a completely new challenge, the actual concept is not totally unrelated to what we have been doing so far,” said Linke.

The strategy of the scientist from Tübingen is so convincing that the Bill & Melinda Gates Foundation recently granted Linke US$ 100,000. The foundation set up by the American computer genius and his wife funds outstanding ideas that focus on the prevention or treatment of infectious diseases. Linke is using the money to finance the two members of his research group who will carry out the bioinformatic and experimental work. If promising results are obtained there is even the possibility of long-term funding.

The Bill & Melinda Gates Foundation is certainly pleased that Linke’s vaccine will be of benefit for the third world population. “I believe that in Africa and Asia more people die of diarrhoea than of malaria every year,” said Linke. A single, cheap vaccine active against several of these pathogens would represent excellent progress. It is not necessary to prevent the disease completely; a mild form of the disease may actually save the lives of many people. In principle, such a vaccine may also prove to be effective against certain types of pneumonia or meningitis that are caused by gram-negative pathogens. And from his own experience, Linke is convinced that “in future it would be good if we could spare holidaymakers from such diseases”.

Further information:
Max Planck Institute for Developmental Biology
Department I - Protein Evolution
Dr. rer. nat. Dirk Linke
Spemannstr. 35
72076 Tübingen
Tel.: +49 (0)7071 601-357
Fax: +49 (0)7071 601-349
E-mail: dirk.linke(at) tuebingen.mpg.de