RESUMO
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.
Assuntos
Proteínas de Bactérias/imunologia , Proteínas de Bactérias/metabolismo , Proteínas de Transporte de Cátions/imunologia , Proteínas de Transporte de Cátions/metabolismo , Infecções Meningocócicas/prevenção & controle , Vacinas Meningocócicas/imunologia , Neisseria meningitidis/metabolismo , Adolescente , Animais , Anticorpos Antibacterianos/sangue , Antígenos de Bactérias/química , Antígenos de Bactérias/genética , Antígenos de Bactérias/imunologia , Antígenos de Bactérias/metabolismo , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Proteínas de Transporte de Cátions/química , Proteínas de Transporte de Cátions/genética , Criança , Pré-Escolar , Feminino , Regulação Bacteriana da Expressão Gênica/fisiologia , Cobaias , Humanos , Lactente , Camundongos , Modelos Moleculares , Neisseria meningitidis/genética , Neisseria meningitidis/imunologia , Filogenia , Conformação Proteica , Ensaios de Anticorpos Bactericidas Séricos , Adulto Jovem , Zinco/metabolismoRESUMO
Neisseria meningitidis may be classified according to the lipooligosaccharide immunotype. We show that this classification can be achieved by PCR genotyping of the genes involved in the lipooligosaccharide inner-core biosynthesis, lpt3, lpt6, lgtG and lot3. Genotyping data correlated well (90-100%) with mass spectrometry data and was, therefore, applied to screen a random subset of recent N. meningitidis serogroup B isolates from Europe. Analysis of the proportion of the different lipooligosaccharide types highlighted the predominance of L3 strains. Surprisingly, high rates of L2 type strains were found in Spain (17%, versus 2.5% in Germany and 1.9% in the United Kingdom). Therefore, we also investigated further these Spanish L2 strains in an attempt to explain such prevalence despite the known sensitivity of L2 immunotype to complement. We explored the hypothesis that these strains express high amounts of factor H-binding protein (fHbp), but we found, on the contrary, that L2 strains express low or undetectable amounts of fHbp. Our findings suggest that, in addition to a genetic analysis, a multivalent approach may be necessary to estimate the effectiveness of a N. meningitidis serogroup B vaccine.
