|Finding New Ways to Fight Meningitis
Factor H Binding Protein: A Novel Vaccine for N. meningiditis B
CHORI scientist Dan Granoff, MD, of the Center for Immunobiology & Vaccine Development, and his colleagues have been making waves recently with their studies of a special lipoprotein, called factor H binding protein (fHbp). This protein just may contain the solution to finding a vaccine for Neisseria meningitidis group B strains, which is a bacteria responsible for meningitis and severe blood stream infections. In a recent spate of nearly a half dozen publications on the subject, Dr. Granoff has proven the viability of fHbp as an exemplary vaccine candidate as well as elucidating critical characteristics of its role in allowing the bacteria to survive in the human blood stream and cause disease.
“The more we understand about what fHbp does, the better we’re able to think about it as a vaccine candidate,” says Dr. Granoff, who has with his colleagues, used the results of their numerous studies to develop a novel vaccine for N. meningitidis B that has demonstrated incredibly broad coverage.
The superiority of fHbp results, in part, from the fact that it targets complement factor H (fH), a molecule that participates in the body’s innate immune system – its natural ability to fight off previously unknown pathogens.
“Complement proteins are a critical component of our innate immune system. If you activate one, it then activates a second, which activates a third, and so on,” explains Dr. Granoff. “The complement system serves a variety of functions, including recognizing foreign substances such as bacteria and allowing them to be killed before the bacteria can cause serious disease.”To prevent the inflammatory responses caused by complement activation from becoming harmful to the host, however, the body also uses “down regulatory” complement molecules to maintain tight regulation over the activation of the complement system. Factor H is one of the most important down-regulatory molecules in the system .
“If you have a vaccine that targets an antigen the bacteria really needs to cause a disease, that means it’s a very good target – the bacteria can’t do with out it,” says Dr. Granoff.
The latest version of Dr. Granoff’s vaccine is made using the outer membrane of mutant bacteria that he and his colleagues engineered to make much higher amounts of fHbp than in the normal bacteria. This vaccine in mice protects against all N. meningitidis B strains. The commercial rights to develop this novel vaccine have been acquired by a pharmaceutical company, with another series of studies planned to confirm its safety and efficacy before clinical trials begin.
Tuesday, May 17, 2011 8:49 AM