An Outer Membrane Vesicle Vaccine for Prevention of Serogroup A and W‐135 Meningococcal Disease in the African Meningitis Belt

Abstract

The bacterium Neisseria meningitidis of serogroups A and W‐135 has in the recent decade caused most of the cases of meningococcal meningitis in the African meningitis belt, and there is currently no efficient and affordable vaccine available demonstrated to protect against both these serogroups. Previously, deoxycholate‐extracted outer membrane vesicle (OMV) vaccines against serogroup B meningococci have been shown to be safe and induce protection in humans in clonal outbreaks. The serogroup A and W‐135 strains isolated from meningitis belt epidemics demonstrate strikingly limited variation in major surface‐exposed protein structures. We have here investigated whether the OMV vaccine strategy also can be applied to prevent both serogroups A and W‐135 meningococcal disease. A novel vaccine combining OMV extracted from recent African serogroup A and W‐135 strains and adsorbed to aluminium hydroxide was developed and its antigenic characteristics and immunogenicity were studied in mice. The specificity of the antibody responses was analysed by immunoblotting and serum bactericidal activity (SBA) assays. Moreover, the bivalent A+W‐135 vaccine was compared with monovalent A and W‐135 OMV vaccines. The bivalent OMV vaccine was able to induce similar SBA titres as the monovalent A or W‐135 OMV towards both serogroups. High SBA titres were also observed against a meningococcal serogroup C strain. These results show that subcapsular antigens may be of importance when developing broadly protective and affordable vaccines for the meningitis belt.

Frequent capsule switching in ‘ultra-virulent’ meningococci – Are we ready for a serogroup B ST-11 complex outbreak?

“…Monovalent OMV preparations have targeted meningococci with PorA subtypes P1.7,16, P1.7-2,4, P1.19,15 and P1.3 13, 14. Multivalent OMV vaccines have also been proposed including a serogroup A + W OMV vaccine incorporating PorA subtypes P1.20,9 and P1.5,2, 15 and a nine-valent formulation including PorA subtypes P1.7,16, P1.22,14, P1.5-1,2-2, P1.5-2,10, P1.7-1,1, P1.12-1,13, P1.19,15-1, P1.7-2,4 and P1.18-1,3 16 …”

Assessment of mOMV adjuvant efficacy in the pathogenic H1N1 influenza virus vaccine

“…Among them, we have developed a promising adjuvant candidate called mOMV which is modified outer membrane vesicles (mOMVs). OMVs are considered as an attractive vaccine adjuvant and antigen delivery platform since they were proven to be effective in human meningococcal vaccine and other experimental vaccines in several countries [17,18]. It is known that wild-type OMV (wOMV) has intrinsic inflammatory potential due to their composition with bacterial cell wall constituents such as lipopolysaccharide (LPS) and peptidoglycan [19].…”

Preclinical immunogenicity study of trivalent meningococcal AWX-OMV vaccines for the African meningitis belt

“…The vaccine antigens were derived from N. meningitidis strains Mk499/03 [22], Mk222/02 [21] and BF2/97 [24,25]; all wild-type disease isolates from Ethiopia and Burkina Faso (Table 1). Three ST-181 MenX strains isolated in 2010: BuFa 9/10, BuFa 19/10, BuFa 24/10 and Ug 3/06, a ST-5403 MenX strain from Uganda in 2006 (Table 1) were used in serum bactericidal assays.…”

“…The LPS content (g LPS/g protein) was characterized by SDS-PAGE followed by silver staining [21]. Antigens were identified by immunoblotting by a panel of monoclonal antibodies as previously described [21].…”

“…We have previously developed a combined MenA http://dx.doi.org/10.1016/j.vaccine.2014.09.063 0264-410X/© 2014 Elsevier Ltd. All rights reserved. and MenW vaccine for the meningitis belt based on OMV [21,22]. This AW-OMV vaccine was shown to be highly immunogenic in mice and induced higher or similar titers of functional antibodies against both MenA and MenW compared with licensed vaccines [22].…”