The group A polysaccharide conjugate vaccine, MenAfriVac, is highly effective at prevention of serogroup A invasive disease and carriage [7], [8] and [9]. However, other serogroups, in particular W and more recently X, are increasingly contributing to the burden of meningococcal disease in sub-Saharan Africa [3], [29], [30], [31] and [32]. Additionally,

other meningococcal serogroups, e.g. group C, that, although not having caused outbreaks in recent years, may become a threat in the future. The challenge for future vaccine approaches for the meningitis belt is to selleck chemical develop a meningococcal vaccine that is not only affordable, but provides broad cross-serogroup protection against meningococcus, and complements the roll out pneumococcal vaccination to deal with the problem of pneumococcal

meningitis in the region. GMMA from recombinant meningococcal strains offer a promising option. They contain protein antigens (e.g. fHbp) which induce antibodies with serogroup independent cross protection. In addition, a simple, economic and scalable procedure for their preparation has been developed with minimal downstream processing required, which enables large quantities of GMMA vaccine to be produced at low cost [10]. While see more strains containing deletions of lpxL1 and capsule synthesis genes with up-regulated fHbp expression have been described [33] and [34], our approach incorporates the additional deletion of gna33 in order to enhance the level of GMMA production, and consequently the potential affordability

of the vaccine for use in Africa. The mechanism of up-regulation of GMMA production is not fully understood. Our findings indicate that GMMA release by different gna33 KO strains is variable, indicating a requirement to screen multiple strains for Isotretinoin high level GMMA release. We tested bactericidal activity of sera from immunised mice against 17 group A, W and X strains. Five μg of the GMMA from the Triple KO, OE fHbp group W strain induced SBA responses against 16 (94%) of these isolates. Ability to kill the A and X strains was attributable to fHbp which comprises only about 3% of the total GMMA protein. In comparison, 5 μg recombinant fHbp ID1 induced a detectable bactericidal antibody response only against one X strain which had the highest level of fHbp expression. This is consistent with previous studies with NOMV demonstrating that fHbp expressed in the native membrane environment induces antibodies with greater functional activity than vaccines containing recombinant fHbp [15], [35] and [36]. Previous studies have demonstrated broad cross-protection of NOMV vaccines against a panel of diverse African strains [15], [34] and [37]. We did not compare our GMMA vaccine directly with NOMV.