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Infect Immun, April 1998, p. 1334-1341, Vol. 66, No. 4
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Intranasal Administration of a Meningococcal Outer Membrane Vesicle Vaccine Induces Persistent Local Mucosal Antibodies and Serum Antibodies with Strong Bactericidal Activity in Humans

Bjørn Haneberg,1,* Rolf Dalseg,1 Elisabeth Wedege,1 E. Arne Høiby,2 Inger Lise Haugen,1 Fredrik Oftung,1 Svein Rune Andersen,1 Lisbeth Meyer Næss,1 Audun Aase,1 Terje E. Michaelsen,1 and Johan Holst1

Department of Vaccinology1 and Department of Bacteriology,2 National Institute of Public Health, N-0403 Oslo, Norway

Received 21 October 1997/Returned for modification 26 November 1997/Accepted 7 January 1998

A nasal vaccine, consisting of outer membrane vesicles (OMVs) from group B Neisseria meningitidis, was given to 12 volunteers in the form of nose drops or nasal spray four times at weekly intervals, with a fifth dose 5 months later. Each nasal dose consisted of 250 µg of protein, 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 responses to OMVs in nasal secretions, and eight developed salivary IgA antibodies which persisted for at least 5 months. Intramuscular immunizations did not lead to antibody responses in the secretions. Modest increases in serum IgG antibodies were obtained in 5 volunteers who had been immunized intranasally, while 10 individuals responded strongly to the intramuscular vaccine. Both the serum and secretory antibody responses 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 after intranasal immunizations was largely similar to that obtained with the intramuscular vaccine. Five and eight vaccinees in the nasal group developed persistent increases in serum bactericidal titers to the homologous meningococcal vaccine strain expressing low and high levels, respectively, of the outer membrane protein Opc. Our results indicate that meningococcal OMVs possess the structures necessary to initiate systemic as well as local mucosal immune responses when presented as a nasal vaccine. Although the serum antibody levels were less conspicuous than those after intramuscular vaccinations, the demonstration of substantial bactericidal activity indicates that a nonproliferating nasal vaccine might induce antibodies of high functional quality.

* Corresponding author. Mailing address: Department of Vaccinology, National Institute of Public Health, P.O. Box 4404 Torshov, N-0403 Oslo, Norway. Phone: 47 22 04 25 01. Fax: 47 22 04 23 01. E-mail: haneberg{at}online.no.




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