title: Outer membrane vesicles (OMVs) and detoxified lipooligosaccharide (dLOS) obtained from Brazilian prevalent N. meningitidis serogroup B strains protect mice against homologous and heterologous meningococcal infection and septic shock.
abstract: Neisseria meningitidis (N. meningitidis) is a serious bacterial pathogen that causes life-threatening invasive bacterial infections especially in children below 2 years of age, teenagers and young adults. We have investigated the protective potential of outer membrane vesicles (OMVs) and detoxified lipooligosaccharide (dLOS) obtained from Brazilian prevalent N. meningitidis serogroup B strains. Swiss mice were immunized with different combinations of OMV and dLOS from N. meningitidis serogroup B strains compared to a reference vaccine (VA-MENGOC-BC), Cuba). The OMVs + dLOS from Brazilian prevalent strains induced higher bactericidal antibody titers against homologous and heterologous target strains and stronger inhibition of thrombocytopenia as compared to the reference vaccine. When the challenge was performed with the B strain, all immunogens tested showed similar survival rates (80%) significantly higher than the control group. Bacterial clearance against the group B strain was comparable for animals immunized with the tested immunogen and the reference vaccine. Inclusion of dLOS from the B strain with the OMV, induced a similar clearance of C strain bacteria as compared to VA-MENGOC-BC. The immunogens, as well as the reference vaccine drastically inhibited increases in TNF-alpha and IL-6 plasma levels after challenge. In conclusion, the OMV/dLOS formulation obtained from Brazilian prevalent strains of N. meningitidis has a remarkable performance protecting mice against the lethal effects of meningococcal challenge showing a good potential as a vaccine and should be considered for clinical evaluation.
authors.affiliation: Laboratório de Tecnologias Bacterianas, Departamento de Desenvolvimento Tecnológico-Bio-Manguinhos, FIOCRUZ, Rio de Janeiro, RJ, Brazil. ellen@bio.fiocruz.br
authors.forename: Ellen
authors.initials: E
authors.lastname: Jessouroun
authors.forename: Ivna F B
authors.initials: IF
authors.lastname: da Silveira
authors.forename: Andréa P
authors.initials: AP
authors.lastname: Larangeira
authors.forename: Solange
authors.initials: S
authors.lastname: Pereira
authors.forename: Solange A
authors.initials: SA
authors.lastname: Fernandes
authors.forename: Leon
authors.initials: L
authors.lastname: Rabinovitch
authors.forename: Carl E
authors.initials: CE
authors.lastname: Frasch
authors.forename: Hugo C
authors.initials: HC
authors.lastname: Castro-Faria-Neto
authors.forename: Patricia T
authors.initials: PT
authors.lastname: Bozza
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis*; D001425:Bacterial Outer Membrane Proteins / Q000008:administration & dosage / Q000032:analysis / Q000276:immunology*; D001428:Bacterial Vaccines; D001938:Brazil; D016207:Cytokines / Q000097:blood; D008070:Lipopolysaccharides / Q000008:administration & dosage* / Q000276:immunology; D008589:Meningococcal Infections / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D009345:Neisseria meningitidis / Q000276:immunology*; D012772:Shock, Septic / Q000276:immunology / Q000517:prevention & control*
chemical_list: D000907:Antibodies, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D016207:Cytokines; D008070:Lipopolysaccharides