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Proof of Principle
CHORI Scientist Developing Novel Vaccine to Combat Emerging Meningitis Strains in Africa

The vaccine has demonstrated extremely broad coverage against the group B strains, and has the potential to be used against other meningitidis strains, including those found in Africa.

In a host of recent publications, CHORI scientist Dan Granoff, MD and his colleagues have elucidated a new vaccine mechanism for prevention of diseases caused by N. meningitidis group B bacteria (called meningococci), one of 5 different bacterial strains that can cause life-threatening meningitis infections all across t all the globe. Whereas most vaccines against meningococcal meningitis have relied on traditional methods that target sugar capsules surrounding the bacteria, this approach couldn't be used to create a group B vaccine because of the risks of eliciting autoimmune responses.

Instead, Dr. Granoff and his colleagues developed a new vaccine approach that targets a special lipoprotein called factor H binding protein (fHbp) (See our April update for more info). The vaccine has demonstrated extremely broad coverage against the group B strains, and has the potential to be used against other meningitidis strains, including those found in Africa.

"Africa has an incredible disease burden where meningitis is concerned, with hundreds of thousands of cases. During epidemics, these cases occur within three or four months, and go from village to village, leaving ten to fifteen percent of the population dead," Dr. Granoff says.

Until recently, most of the meningococcal meningitis epidemics in Africa were caused by group A strains, for which Dr. Granoff already helped develop a traditional vaccine that uses the group A sugar capsule. However, additional strains recently emerged in the continent as well - N. meningitidis capsular groups W-135 and X. In Burkina Faso, a relatively small country, there were 30 thousand cases in 3 months caused by W-135 bacteria, and in a region of Nigeria, there were 5 thousand cases caused by group X bacteria.

"It may seem like small potatoes compared to the number of deaths caused by group A strains, but we really worry that if the group A vaccine proves successful, we may just end up with an emergence of these other strains instead," says Dr. Granoff.

The cost of creating a vaccine against W-135 and X N. meningitidis strains in Africa using traditional methods will be very large and will take many years. Developing an inexpensive group A vaccine alone, which was made possible by a 70 million dollar grant from the Bill & Melinda Gates Foundation, took a decade. With the development of the new vaccine approach against group B strains, however, Dr. Granoff believes it might be possible to have an inexpensive and simpler vaccine for Africa based on the new approach.

The new approach used outer membrane vesicles (OMV) from mutant group B meningococcal bacteria, which were engineered to over-express fHbp. In an article published in the May 1st edition of the Journal of Infectious Diseases, Dr. Granoff describes using the OMV approach they developed for group B strains to create a new vaccine against the N. meningitidis strains found predominantly in Africa.
"Calling the current vaccine we've developed a group B vaccine is really a misnomer. If the principle works for group B, it should work against strains with other capsular groups as well."
"We got a terrific collection of strains from Africa representing isolates that caused every major meningitis epidemic in the continent over the last 50 years," explains Dr. Granoff of the new study. "We were able to look at the fHbp genes and proteins expressed by these strains, and discovered it's really a very small number of fHbp variants that have remained remarkably stable through the years."

In addition, Dr. Granoff and his colleagues discovered that the OMV vaccines with fHpb antigens developed to protect against N. meningitidis group B strains, actually worked against all of the African group A, W-135 and X strains tested.

"If we could do that well a vaccine prepared from just two group B mutants, what would happen if we took group A and W-135 strains from African epidemics and created similar mutants as we did for group B but matched the fHbp antigens in the vaccine for those expressed by African strains? We might be able to come up with a terrific vaccine for Africa," says Dr. Granoff.
As a result of such positive indications, Dr. Granoff and his colleagues already have a new grant proposal in submission and efforts are well underway to make the latest vaccine venture with fHbp as successful as the last.

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Tuesday, May 17, 2011 8:19 AM

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