title: Safety and immunogenicity testing of an intranasal group B meningococcal native outer membrane vesicle vaccine in healthy volunteers.
abstract: An intranasal vaccine composed of native outer membrane vesicles (NOMV) not exposed to detergent or denaturing agents was prepared from the group B meningococcal strain 9162 SynX(-)(-:15:P1.3:P5.10,11:L3,7,9) and tested in 32 healthy adult volunteers. Four groups of 8 volunteers were vaccinated intranasally with three doses of vaccine. The vaccine was very well tolerated in all dosing groups, despite the presence of lipo-oligosaccharide in the vaccine at a level of 25% relative to protein. The antibody response as measured by ELISA in serum, saliva and nasal wash fluids was relatively low in all 4 groups, but the induced serum antibodies had strong bactericidal activity. Persistent bactericidal antibodies (> or =4-fold increase) were produced in 75% of the recipients. Some of the bactericidal antibodies were cross reactive against divergent group B strains. Most of the bactericidal antibodies appeared to be specific for PorA and L3,7,9 LOS. The vaccine also produced a local antibody response which was detected in the nasal wash fluids of volunteers. These data suggest that nasal immunization with NOMV is a safe and effective approach to induce systemic and local immunity against the group B meningococcus and deserves further study.
authors.affiliation: Department of Bacterial Diseases, Walter Reed Army Institute of Research, Washington, DC 20307-5100, USA. ltc_joseph_drabick_at_wramc16-washdc@wramc1-amedd.army.mil
authors.forename: J J
authors.initials: JJ
authors.lastname: Drabick
authors.forename: B L
authors.initials: BL
authors.lastname: Brandt
authors.forename: E E
authors.initials: EE
authors.lastname: Moran
authors.forename: N B
authors.initials: NB
authors.lastname: Saunders
authors.forename: D R
authors.initials: DR
authors.lastname: Shoemaker
authors.forename: W D
authors.initials: WD
authors.lastname: Zollinger
mesh_terms: D000281:Administration, Intranasal; D000328:Adult; D000368:Aged; D000907:Antibodies, Bacterial / Q000096:biosynthesis / Q000276:immunology; D000918:Antibody Specificity; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D001770:Blood Bactericidal Activity; D005260:Female; D006801:Humans; D007114:Immunization; D007070:Immunoglobulin A / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D008875:Middle Aged; D013292:Streptococcus agalactiae / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D008070:Lipopolysaccharides; C023023:lipid-linked oligosaccharides