The development of a meningococcal disease vaccine based onNeisseria lactamicaouter membrane vesicles

Serogroup B meningococcal disease remains a serious problem in many countries and no effective vaccine is currently available. Immunological and epidemiological evidence suggests that carriage of commensalNeisseriaspecies is involved in the development of natural immunity against meningococcal disease.Neisseria lactamicahas many surface structures in common withNeisseria meningitidisand may be the most important of these species. We have produced extensive pre-clinical data, which indicate thatN. lactamicaouter membrane vesicles (OMVs) may provide a vaccine effective against diverse disease-causing meningococcal strains. Immunisation withN. lactamicaOMVs protected against lethal challenge with diverse meningococcal isolates in a mouse intraperitoneal challenge model of meningococcal disease and we are developing this vaccine for use in a phase I safety and immunogenicity study in adult volunteers. We have shown that OMVs produced from bacteria grown under iron-limited or iron-rich conditions provide equivalent protection in the mouse infection model and thus OMVs produced from iron-rich will be used. Sterile filtration ofN. lactamicaOMVs has proved difficult but this has been improved by resuspending the vesicles in a buffer, which increases their surface zeta potential. The vaccine is currently being manufactured and validated ELISA protocols have been developed for the analysis of serological responses.