A meningococcal NOMV-FHbp vaccine for Africa elicits broader serum bactericidal antibody responses against serogroup B and non-B strains than a licensed serogroup B vaccine

Abstract

Background Meningococcal epidemics in Sub-Sahara caused by serogroup A strains are controlled by a group A polysaccharide conjugate vaccine. Strains with serogroups C, W and X continue to cause epidemics. Protein antigens in licensed serogroup B vaccines are shared among serogroup B and non-B strains. Purpose Compare serum bactericidal antibody responses elicited by an investigational native outer membrane vesicle vaccine with over-expressed Factor H binding protein (NOMV-FHbp) and a licensed serogroup B vaccine (MenB-4C) against African serogroup A, B, C, W and X strains. Methods Human Factor H (FH) transgenic mice were immunized with NOMV-FHbp prepared from a mutant African meningococcal strain containing genetically attenuated endotoxin and a mutant sub-family B FHbp antigen with low FH binding, or with MenB-4C, which contains a recombinant sub-family B FHbp antigen that binds human FH, and three other antigens, NHba, NadA and PorA P1.4, capable of eliciting bactericidal antibody. Results The NOMV-FHbp elicited serum bactericidal activity against 12 of 13 serogroup A, B, W or X strains from Africa, and four isogenic serogroup B mutants with subfamily B FHbp sequence variants. There was no activity against a serogroup B mutant with sub-family A FHbp, or two serogroup C isolates from a recent outbreak in Northern Nigeria, which were mismatched for both PorA and sub-family of the FHbp vaccine antigen. For MenB-4C, NHba was expressed by all 16 African isolates tested, FHbp sub-family B in 13, and NadA in five. However, MenB-4C elicited titers ≥1:10 against only one isolate, and against only two of four serogroup B mutant strains with sub-family B FHbp sequence variants. Conclusions NOMV-FHbp has greater potential to confer serogroup-independent protection in Africa than the licensed MenB-4C vaccine. However, the NOMV-FHbp vaccine will require inclusion of sub-family A FHbp for coverage against recent serogroup C strains causing outbreaks in Northern Nigeria.

Meningococcal carriage in high-risk settings: A systematic review

“…A, B, C, W, and Y, although the 'B' vaccines include recombinant proteins or recombinant proteins plus outer membrane vesicles, not capsular polysaccharides like the other vaccines. While conjugate vaccines have induced herd immunity for some serogroups, in part through a reduction in carriage levels (Trotter and Maiden, 2009), it is as yet unclear whether the broad-protection MenB vaccines will have similar effects (Donnelly et al, 2010;Pajon et al, 2016). Knowledge of the locally circulating serogroups and disease incidence is key for appropriate vaccine recommendations.…”

Enhanced protective antibody to a mutant meningococcal factor H-binding protein with low-factor H binding

“…CH860 has FHbp ID 15 (87% identical to FHbp ID 1). We also tested serum anti-FHbp bactericidal antibody responses against 2 previously described mutants of strain H44/76, one in which the gene encoding the native FHbp ID 1 had been replaced by subfamily B FHbp ID 13 (93% amino acid identity with ID 1) (54) and one in which was engineered to have ~50% lower expression of FHbp ID 1 than in the parental WT strain (30). …”

Spheres of Hope, Packets of Doom: the Good and Bad of Outer Membrane Vesicles in Interspecies and Ecological Dynamics

“…OMVs from a variety of bacteria have broad effects on animal immune responses (reviewed in reference 89). Native and modified OMVs have been implemented as vaccines against pathogens, such as Salmonella enterica serovar Typhimurium and Vibrio cholerae, in animal models (26,90,91) and have reached clinical usage against Neisseria meningitidis (92)(93)(94). Due to the size of OMVs, visualizing them in situ has generally required electron microscopy of fixed material, but improvements in superresolution techniques hold promise for tracking OMVs, their contents, and their interactions in living environments.…”