title: A phase 1 study of a meningococcal native outer membrane vesicle vaccine made from a group B strain with deleted lpxL1 and synX, over-expressed factor H binding protein, two PorAs and stabilized OpcA expression.
abstract: This phase I clinical trial assessed the safety and immunogenicity of a native outer membrane vesicle (NOMV) vaccine prepared from an lpxL1(-) synX(-) mutant of strain 8570(B:4:P1.19,15:L8-5) of Neisseria meningitidis. Additional mutations enhance the expression of factor H binding protein variant 1 (fHbp v.1), stabilize expression of OpcA and introduce a second PorA (P1.22,14). Thirty-six volunteers were assigned to one of four dose groups (10, 25, 50 and 75 mcg, based on protein content) to receive three intramuscular injections at six week intervals with aluminum hydroxide adjuvant. Specific local and systemic adverse events were solicited by diary and at visits on days 2, 7, and 14 after each vaccination. Blood chemistries, complete blood count, and coagulation studies were measured on each vaccination day and again 2 and 14 days later. Blood for ELISA and serum bactericidal assays was drawn two and six weeks after each vaccination. The proportion of volunteers who developed a fourfold or greater increase in bactericidal activity to the wild type parent of the vaccine strain at two weeks after the third dose was 27 out of 34 (0.79, 95% C.I. 0.65-0.93). Against four other group B strains the response rate ranged from 41% to 82% indicating a good cross reactive antibody response. Depletion assays show contributions to bactericidal activity from antibodies to lipooligosaccharide (LOS), fHbp v.1 and OpcA.
authors.affiliation: Walter Reed Army Institute of Research (WRAIR), Silver Spring, MD, USA. paul.keiser@us.army.mil
authors.forename: P B
authors.initials: PB
authors.lastname: Keiser
authors.forename: S
authors.initials: S
authors.lastname: Biggs-Cicatelli
authors.forename: E E
authors.initials: EE
authors.lastname: Moran
authors.forename: D H
authors.initials: DH
authors.lastname: Schmiel
authors.forename: V B
authors.initials: VB
authors.lastname: Pinto
authors.forename: R E
authors.initials: RE
authors.lastname: Burden
authors.forename: L B
authors.initials: LB
authors.lastname: Miller
authors.forename: J E
authors.initials: JE
authors.lastname: Moon
authors.forename: R A
authors.initials: RA
authors.lastname: Bowden
authors.forename: J F
authors.initials: JF
authors.lastname: Cummings
authors.forename: W D
authors.initials: WD
authors.lastname: Zollinger
mesh_terms: D000217:Acyltransferases / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood; D000917:Antibody Formation; D000942:Antigens, Bacterial / Q000276:immunology*; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D003429:Cross Reactions; D005260:Female; D020868:Gene Silencing; D006801:Humans; D007117:Immunization, Secondary; D008297:Male; D008585:Meningitis, Meningococcal / Q000276:immunology / Q000517:prevention & control*; D022401:Meningococcal Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D008875:Middle Aged; D009154:Mutation; D038541:Neisseria meningitidis, Serogroup B / Q000235:genetics / Q000276:immunology; D018272:Porins / Q000276:immunology*; D019998:Racemases and Epimerases / Q000235:genetics; D058248:Serum Bactericidal Antibody Assay; D055815:Young Adult
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D022401:Meningococcal Vaccines; C505154:OpcA protein, Neisseria meningitidis; D018272:Porins; C484699:factor H-binding protein, Neisseria meningitidis; C057699:porin protein, Neisseria; D000217:Acyltransferases; C118473:LpxL protein, bacteria; D019998:Racemases and Epimerases; C091606:NeuC protein, Neisseria meningitidis