Meningococcal outer membrane vesicle vaccine given intranasally can induceimmunological memory and booster responses without evidence of tolerance

We have studied the ability of outer membrane vesicle (OMV) vaccines from N eisseria meningitidis serogroup B to induce vaccine-specific antibody and s pleen cell proliferative responses in mice after being administered intrana sally (i.n.) and/or subcutaneously (s.c.). A series of four weekly i.n. dos es (25 mug) without adjuvant or a single s.c. dose (2.5 mug) with aluminum hydroxide was followed 2 months later by secondary i.n. or s.c. immunizatio ns. After i.n. priming, both immunoglobulin G (IgG) antibody responses in s erum, measured by enzyme-linked immunosorbent assay, and IgA antibodies in saliva and extracts of feces were significantly boosted by later i.n. immun izations. The IgG antibody responses in serum were also significantly augme nted by secondary s.c. immunization after i.n. as well as s.c. priming. Ser a 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 antib ody responses in secretions to later i.n. immunizations. The i.n. immunizat ions also led to marked OMV-specific spleen cell proliferation in vitro. Bo th serum antibody responses and spleen cell proliferation were higher after i.n. priming and later s.c. immunizations than after s.c. immunizations al one. 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 nonp roliferating meningococcal OMV vaccine given i.n. can induce immunological memory and that it may be favorably combined with similar vaccines for inje ctions.