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Army

Group B meningitis vaccine

Multivalent vaccine candidate with multiple meningococcal antigens, each with capacity to induce bactericidal antibodies

Medical & Biotechnology

Neisseria meningitidis is a major cause of meningitis and septicemia worldwide. Meningococcal meningitis is an inflammation of the meninges, the membrane lining the brain and the spinal cord. In both meningococcal septicemia and meningococcal meningitis, damage is caused by an uncontrolled localized or systemic host inflammatory response. Group B meningococcal disease currently accounts for at least half of all meningococcal disease in many countries in North and South America and Europe. A virulent clone of group B N. meningitidis known as ET5, which emerged in Norway in the late 1970s, has been responsible for prolonged epidemics in Norway, Cuba, Brazil, and Chile.

Vaccines against N. meningitidis serogroups A, C, Y, and W135 are available and routinely used with excellent results. A suitable vaccine against group B strains has been more difficult to develop for a variety of reasons. The capsular polysaccharide that defines the serogroup is ineffective and potentially unsafe for use in a vaccine because it has the same structure as polysialic acid found on certain human cells, specifically blood cells. Further, subcapsular antigens that are surface-exposed, such as outer membrane proteins and lipooligosaccharide (LOS), are antigenically variable and/or inconsistently expressed among group B strains. No single antigen has been identified that alone has all the characteristics essential to developing an effective vaccine.

To fill this void in our vaccine arsenal, Army researchers have developed a candidate vaccine using native outer membrane vesicles (NOMVs) obtained from at least two meningococcal strains genetically modified to provide broad-based protection. The NOMVs include three different sets of antigens based on PorA, LOS, and conserved outer membrane proteins. The genetically modified bacterial strains also were modified to provide enhanced safety by inactivation of the lpxL1, synX, and lgtA genes. The Army vaccine includes a different conserved surface protein with demonstrated capacity to induce bactericidal antibodies in each strain.

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