title: ZnuD, a potential candidate for a simple and universal Neisseria meningitidis vaccine.
abstract: Neisseria meningitidis serogroup B (MenB) is a major cause of bacterial sepsis and meningitis, with the highest disease burden in young children. Available vaccines are based on outer membrane vesicles (OMVs) obtained from wild-type strains. However, particularly in toddlers and infants, they confer protection mostly against strains expressing the homologous protein PorA, a major and variable outer membrane protein. In the quest for alternative vaccine antigens able to provide broad MenB strain coverage in younger populations, but potentially also across all age groups, ZnuD, a protein expressed under zinc-limiting conditions, may be considered a promising candidate. Here, we have investigated the potential value of ZnuD and show that it is a conserved antigen expressed by all MenB strains tested except for some strains of clonal complex ST-8. In mice and guinea pigs immunized with ZnuD-expressing OMVs, antibodies were elicited that were able to trigger complement-mediated killing of all the MenB strains and serogroup A, C, and Y strains tested when grown under conditions of zinc limitation. ZnuD is also expressed during infection, since anti-ZnuD antibodies were detected in sera from patients. In conclusion, we confirm the potential of ZnuD-bearing OMVs as a component of an effective MenB vaccine.
authors.affiliation: Institute for Hygiene and Microbiology, University of Würzburg, Würzburg, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Hubert
authors.forename: Nathalie
authors.initials: N
authors.lastname: Devos
authors.forename: Ines
authors.initials: I
authors.lastname: Mordhorst
authors.forename: Christine
authors.initials: C
authors.lastname: Tans
authors.forename: Guy
authors.initials: G
authors.lastname: Baudoux
authors.forename: Christiane
authors.initials: C
authors.lastname: Feron
authors.forename: Karine
authors.initials: K
authors.lastname: Goraj
authors.forename: Jan
authors.initials: J
authors.lastname: Tommassen
authors.forename: Ulrich
authors.initials: U
authors.lastname: Vogel
authors.forename: Jan T
authors.initials: JT
authors.lastname: Poolman
authors.forename: Vincent
authors.initials: V
authors.lastname: Weynants
mesh_terms: D000293:Adolescent; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D027682:Cation Transport Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D005260:Female; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D006168:Guinea Pigs; D006801:Humans; D007223:Infant; D008589:Meningococcal Infections / Q000517:prevention & control*; D022401:Meningococcal Vaccines / Q000276:immunology*; D051379:Mice; D008958:Models, Molecular; D009345:Neisseria meningitidis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D010802:Phylogeny; D011487:Protein Conformation; D058248:Serum Bactericidal Antibody Assay; D055815:Young Adult; D015032:Zinc / Q000378:metabolism
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D027682:Cation Transport Proteins; D022401:Meningococcal Vaccines; C553584:ZnuD protein, Neisseria meningitidis; D015032:Zinc