title: Meningococcal outer membrane vesicle vaccine given intranasally can induce immunological memory and booster responses without evidence of tolerance.
abstract: We have studied the ability of outer membrane vesicle (OMV) vaccines from Neisseria meningitidis serogroup B to induce vaccine-specific antibody and spleen cell proliferative responses in mice after being administered intranasally (i.n.) and/or subcutaneously (s.c.). A series of four weekly i.n. doses (25 microg) without adjuvant or a single s.c. dose (2.5 microg) with aluminum hydroxide was followed 2 months later by secondary i.n. or s.c. immunizations. After i.n. priming, both immunoglobulin G (IgG) antibody responses in serum, measured by enzyme-linked immunosorbent assay, and IgA antibodies in saliva and extracts of feces were significantly boosted by later i.n. immunizations. The IgG antibody responses in serum were also significantly augmented by secondary s.c. immunization after i.n. as well as s.c. priming. Sera from mice immunized i.n. reached the same level of bactericidal activity as after s.c. immunizations. The s.c. immunizations alone, however, had no effect on mucosal IgA antibody responses, but could prime for booster antibody responses in secretions to later i.n. immunizations. The i.n. immunizations also led to marked OMV-specific spleen cell proliferation in vitro. Both serum antibody responses and spleen cell proliferation were higher after i.n. priming and later s.c. immunizations than after s.c. immunizations alone. There was thus no evidence that i.n. priming had induced immunological tolerance within the B- or T-cell system. Our results indicate that a nonproliferating meningococcal OMV vaccine given i.n. can induce immunological memory and that it may be favorably combined with similar vaccines for injections.
authors.affiliation: Department of Vaccinology, National Institute of Public Health, N-0403 Oslo, Norway.
authors.forename: H
authors.initials: H
authors.lastname: Bakke
authors.forename: K
authors.initials: K
authors.lastname: Lie
authors.forename: I L
authors.initials: IL
authors.lastname: Haugen
authors.forename: G E
authors.initials: GE
authors.lastname: Korsvold
authors.forename: E A
authors.initials: EA
authors.lastname: Høiby
authors.forename: L M
authors.initials: LM
authors.lastname: Naess
authors.forename: J
authors.initials: J
authors.lastname: Holst
authors.forename: I S
authors.initials: IS
authors.lastname: Aaberge
authors.forename: F
authors.initials: F
authors.lastname: Oftung
authors.forename: B
authors.initials: B
authors.lastname: Haneberg
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis / Q000097:blood; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D002455:Cell Division; D005260:Female; D007108:Immune Tolerance / Q000276:immunology*; D018928:Immunity, Mucosal / Q000276:immunology; D007117:Immunization, Secondary; D007156:Immunologic Memory / Q000276:immunology*; D007279:Injections, Subcutaneous; D022401:Meningococcal Vaccines / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009345:Neisseria meningitidis / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D001425:Bacterial Outer Membrane Proteins; D022401:Meningococcal Vaccines