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Infect Immun, April 1998, p. 1334-1341, Vol. 66, No. 4
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.
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
*
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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