%0 Journal Article %1 hubert_znud_2013 %A Hubert, Kerstin %A Devos, Nathalie %A Mordhorst, Ines %A Tans, Christine %A Baudoux, Guy %A Feron, Christiane %A Goraj, Karine %A Tommassen, Jan %A Vogel, Ulrich %A Poolman, Jan T %A Weynants, Vincent %D 2013 %J Infection and immunity %K Adolescent Animals Antibodies Antigens Bacterial Bacterial_Proteins Cation_Transport_Proteins Child Female Gene_Expression_Regulation Guinea_Pigs Humans Infant Meningococcal_Infections Meningococcal_Vaccines Mice Models Molecular Neisseria_meningitidis Phylogeny Preschool Protein_Conformation Serum_Bactericidal_Antibody_Assay Young_Adult Zinc serum_resistance %N 6 %P 1915--1927 %R 10.1128/IAI.01312-12 %T ZnuD, a potential candidate for a simple and universal Neisseria meningitidis vaccine %V 81 %X 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.

@article{hubert_znud_2013, 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.}, added-at = {2013-10-04T09:46:01.000+0200}, author = {Hubert, Kerstin and Devos, Nathalie and Mordhorst, Ines and Tans, Christine and Baudoux, Guy and Feron, Christiane and Goraj, Karine and Tommassen, Jan and Vogel, Ulrich and Poolman, Jan T and Weynants, Vincent}, biburl = {https://www.bibsonomy.org/bibtex/28f9c9305086486147753092d0dd77c6d/ag_vogel}, doi = {10.1128/IAI.01312-12}, interhash = {56d9c4728862a410c4edc7cd3b8f622c}, intrahash = {8f9c9305086486147753092d0dd77c6d}, issn = {1098-5522}, journal = {Infection and immunity}, keywords = {Adolescent Animals Antibodies Antigens Bacterial Bacterial_Proteins Cation_Transport_Proteins Child Female Gene_Expression_Regulation Guinea_Pigs Humans Infant Meningococcal_Infections Meningococcal_Vaccines Mice Models Molecular Neisseria_meningitidis Phylogeny Preschool Protein_Conformation Serum_Bactericidal_Antibody_Assay Young_Adult Zinc serum_resistance}, language = {eng}, month = jun, note = {{PMID:} 23509142}, number = 6, pages = {1915--1927}, timestamp = {2013-10-04T09:46:01.000+0200}, title = {{ZnuD}, a potential candidate for a simple and universal Neisseria meningitidis vaccine}, volume = 81, year = 2013 }