title: Phase I safety and immunogenicity study of a candidate meningococcal disease vaccine based on Neisseria lactamica outer membrane vesicles.
abstract: Natural immunity to meningococcal disease in young children is associated epidemiologically with carriage of commensal Neisseria species, including Neisseria lactamica. We have previously demonstrated that outer membrane vesicles (OMVs) from N. lactamica provide protection against lethal challenge in a mouse model of meningococcal septicemia. We evaluated the safety and immunogenicity of an N. lactamica OMV vaccine in a phase I placebo-controlled, double-blinded clinical trial. Ninety-seven healthy young adult male volunteers were randomized to receive three doses of either an OMV vaccine or an Alhydrogel control. Subsequently, some subjects who had received the OMV vaccine also received a fourth dose of OMV vaccine, 6 months after the third dose. Injection site reactions were more frequent in the OMV-receiving group, but all reactions were mild or moderate in intensity. The OMV vaccine was immunogenic, eliciting rises in titers of immunoglobulin G (IgG) against the vaccine OMVs, together with a significant booster response, as determined by an enzyme-linked immunosorbent assay. Additionally, the vaccine induced modest cross-reactive immunity to six diverse strains of serogroup B Neisseria meningitidis, including IgG against meningococcal OMVs, serum bactericidal antibodies, and opsonophagocytic activity. The percentages of subjects showing > or =4-fold rises in bactericidal antibody titer obtained were similar to those previously reported for the Norwegian meningococcal OMV vaccine against the same heterologous meningococcal strain panel. In conclusion, this N. lactamica OMV vaccine is safe and induces a weak but broad humoral immune response to N. meningitidis.
authors: Health Protection Agency, Centre for Emergency Preparedness and Response, Porton Down, Salisbury, UK. andrew.gorringe@hpa.org.uk
authors: Andrew R
authors: AR
authors: Gorringe
authors: Stephen
authors: S
authors: Taylor
authors: Charlotte
authors: C
authors: Brookes
authors: Mary
authors: M
authors: Matheson
authors: Michelle
authors: M
authors: Finney
authors: Moyra
authors: M
authors: Kerr
authors: Michael
authors: M
authors: Hudson
authors: Jamie
authors: J
authors: Findlow
authors: Ray
authors: R
authors: Borrow
authors: Nick
authors: N
authors: Andrews
authors: George
authors: G
authors: Kafatos
authors: Cariad M
authors: CM
authors: Evans
authors: Robert C
authors: RC
authors: Read
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000293:Adolescent; D000328:Adult; D000536:Aluminum Hydroxide / Q000008:administration & dosage; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D003429:Cross Reactions; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006805:Human Experimentation; D006801:Humans; D007117:Immunization, Secondary / Q000379:methods; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D008297:Male; D022401:Meningococcal Vaccines / Q000009:adverse effects* / Q000276:immunology*; D051379:Mice; D008875:Middle Aged; D042806:Neisseria lactamica / Q000276:immunology*; D009345:Neisseria meningitidis / Q000276:immunology; D009895:Opsonin Proteins / Q000097:blood / Q000276:immunology; D010919:Placebos / Q000008:administration & dosage; D022142:Secretory Vesicles / Q000276:immunology*; D055815:Young Adult
chemical_list: D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D001425:Bacterial Outer Membrane Proteins; D007074:Immunoglobulin G; D022401:Meningococcal Vaccines; D009895:Opsonin Proteins; D010919:Placebos; D000536:Aluminum Hydroxide