Deadly meningitis B, a disease that mainly targets children, has had its secrets laid bare by the latest genomic techniques.
快猫短视频s used computers to sift through the genetic blueprint of the meningococcus bug that causes the disease. This revealed over 80 proteins that could be used to make an effective meningitis B vaccine. What鈥檚 more, the toxin that causes the disease鈥檚 deadly damage could itself become a vaccine target.
There is already an effective vaccine against the bug that causes meningitis C. But attempts to develop a vaccine against meningococcus B have been fraught with problems.
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Meningococcus B comes in many different guises. Also, the outer coating of the bacterium doesn鈥檛 provoke much of an immune response. And vaccines that use parts of the bacterium鈥檚 cell membrane don鈥檛 protect children under the age of four. Doctors also fear that the proteins in such vaccines may not give protection against all strains of meningococcus B.
An international consortium of scientists decided to attack meningococcus B with state-of-the-art genomics and bioinformatics. Researchers from the biotech company Chiron in Siena, Italy, the University of Oxford and The Institute for Genomic Research (TIGR) in Rockville, Maryland, first sequenced the bug鈥檚 genome.
They then trawled through the gene sequences, searching for proteins that looked as if they would be present on the surface of the bacterium, where they are easy for the immune system to see.
The team then made some of the proteins and injected them into mice. Sure enough, some of the mice made antibodies which were capable of killing the bacterium in the test tube.
But there鈥檚 a catch. Meningococcus is expert at evading the immune system. 鈥淭his organism is probably one of the best chameleons in the business,鈥� says Richard Moxon, who leads the Oxford group.
It constantly changes its disguise by varying the shape of parts of the proteins on its surface. Any vaccine would have to take this into account, and also be able to target all strains.
So the researchers compared the gene sequences of these proteins in 30 meningococcus B strains. Sequences that are the same in all the strains highlight parts of the proteins that have stayed the same over the course of evolution. These reveal which parts of the proteins are critical to their function, because they can鈥檛 be tinkered with.
The researchers narrowed down their list of proteins to 80 promising candidates, which they are looking at in detail. It鈥檚 unlikely that any single protein will be a magic bullet against meningococcus B. 鈥淚 think that the ideal vaccine will be a multi-component one,鈥� says Moxon.
Together with colleagues at the National Research Council in Ottawa, Moxon鈥檚 team in Oxford is also looking at turning the bacterium鈥檚 weapons on itself. The meningococcus bug does its damage by producing a type of bacterial toxin known as a lipopolysaccharide (LPS), and this could itself be used to make a vaccine, says Moxon.
The outer part of the LPS molecule is highly variable, but the inner part is not. Until now, scientists thought that this inner core was hidden from the immune system. But the researchers have found that they can make antibodies that attack it.
A number of other bacteria also produce LPS toxins, so the strategy could be used against the diseases they cause. But Moxon stresses that this reseach still has a long way to go: 鈥淲e still have mountains to climb,鈥� he says.
The research was presented at the 40th Interscience Conference on Antimicrobial Agents and Chemotherapy in Toronto, Canada. For more stories from the conference visit www.newscientist.com/conferences/conflist.jsp?conf=ICAAC200009.