INTRANASAL ADMINISTRATION OF A MENINGOCOCCAL OUTER-MEMBRANE VESICLE VACCINE INDUCES PERSISTENT LOCAL MUCOSAL ANTIBODIES AND SERUM ANTIBODIES WITH STRONG BACTERICIDAL ACTIVITY IN HUMANS

A nasal vaccine, consisting of outer membrane vesicles (OMVs) from gro up B Neisseria meningitidis, was given to 12 volunteers in the form of nose drops or nasal spray four times at weekly intervals, with a fift h dose 5 months later, Each nasal dose consisted of 250 mu g of protei n, equivalent to 10 times the intramuscular dose that was administered twice with a 6-week interval to 11 other volunteers. All individuals given the nasal vaccine developed immunoglobulin A (IgA) antibody resp onses to OMVs in nasal secretions, and eight developed salivary IgA an tibodies which persisted for at least 5 months, Intramuscular immuniza tions did not lead to antibody responses in the secretions. Modest inc reases in serum IgG antibodies were obtained in 5 volunteers who had b een immunized intranasally, while 10 individuals responded strongly to the intramuscular vaccine. Both the serum and secretory antibody resp onses reached a maximum after two to three doses of the nasal vaccine, with no significant booster effect of the fifth dose, The pattern of serum antibody specificities against the different OMV components afte r intranasal immunizations was largely similar to that obtained with t he intramuscular vaccine. Five and eight vaccinees in the nasal group developed persistent increases in serum bactericidal titers to the hom ologous meningococcal vaccine strain expressing low and high levels, r espectively, of the outer membrane protein Ope. Our results indicate t hat meningococcal OMVs possess the structures necessary to initiate sy stemic as well as local mucosal immune responses when presented as a n asal vaccine. Although the serum antibody levels were less conspicuous than those after intramuscular vaccinations, the demonstration of sub stantial bactericidal activity indicates that a nonproliferating nasal vaccine might induce antibodies of high functional quality.