Newspapers in the UK are buzzing with excitement over news that a new vaccine against meningitis B developed by the Swiss pharmaceuticals firm Novartis has performed well in early clinical trials.
About 3,000 mostly young people catch meningitis B every year in the USA, of whom about 10% die and 25% suffer lifelong injuries, so an effective vaccine is highly desirable. Until now efforts to prevent meningitis B have been hampered by the fact that existing vaccines only protect against a few of the numerous different type B strains of the bacterium Neisseria meningitidis that cause the disease, so the development of a universal vaccine that is potentially effective against a wide range of bacterial strains is a significant advance (1).
The development of the new vaccine is also noteworthy because of how it was done. Vaccine development relies on identifying parts of the bacterium known as antigens that can act as targets for the immune system. Rather than using the usual method of attempting to isolate bacterial protein that might act as antigens the Novartis team led by Dr. Mariagrazia Pizza adopted a “reverse vaccinology” approach where they searched the Neisseria meningitidis genome for genes that encoded proteins that might be useful antigens. They identified over 300 potential antigens, and the next step was to screen these for their ability to stimulate the immune system to produce antibodies that kill bacteria in vitro. This required an intact functioning mammalian immune system, so the researchers used mice (2).
The mice were injected with candidate antigens and later antibodies were harvested from the mice and tested for their bactericidal activity against three distinct strains of Neisseria meningitidis, identifying twenty eight antigens that induced the production of bactericidal antibodies. However none of these 28 antigens were potent enough to be used alone in a universal vaccine, so the researchers next assessed various combinations of the most promising antigens. A vaccine containing 5 antigens was found to induce the production of antibodies that had excellent bactericidal activity against all three strains of Neisseria meningitidis. The multicomponent vaccine was then tested against a panel of 85 type B Neisseria meningitidis strains that represent the global diversity of the bacterium, and was found to be effective against almost all strains, especially the most lethal strains. To check that the bactericidal activity in vitro correlated to an ability to prevent disease rats which had been infected with Neisseria meningitidis were treated with serum containing antibodies from vaccinated mice. Rats that were treated with serum were fully protected, a result that provided good evidence that the multicomponent vaccine works.
This vaccine has now been assessed in human trials involving 150 children, and found to safely stimulate the production of antibodies that kill Neisseria meningitidis. Of course it still remains to be determined if this vaccine does protect against a wide range of meningitis B strains in the field, and larger clinical trials to evaluate this are underway, but the results so far are very promising.
1) Novartis press release, May 14 2008. http://www.novartis.com/newsroom/media-releases/en/2008/1218899.shtml
2) Giuliani M.M. et al. “A universal vaccine for serogroup B meningococcus” Proc Natl Acad Sci U S A. Volume 103, Issue 29, pages 10834-10839 (2006).