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 g) without adjuvant or a single s.c. dose (2.5 g) 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.

Local and Systemic Antibody Responses in Mice Immunized Intranasally with Native and Detergent-Extracted Outer Membrane Vesicles fromNeisseria meningitidis

“…with four weekly doses of the Norwegian DOMV vaccine, SBA titers did not increase after a new round of i.n. immunizations (9). We have previously made similar observations when mice were immunized with NOMVs (unpublished results).…”

“…Interestingly, a significant increase in SBA titer was found in mice primed i.n. and boosted subcutaneously with one dose of DOMV vaccine (9). Whether humans would benefit from this immunization schedule for OMV vaccines remains to be determined.…”

Intranasal Vaccination against Cutaneous Leishmaniasis with a Particulated Leishmanial Antigen or DNA Encoding LACK

“…Intestinal or nasal antigen uptake may result in peripheral tolerance, and this was the starting point of the present work with disease-promoting parasite antigens. However, systemic immunity may also be achieved after antigen administration through the mucosa (1), and the balance between tolerance and immunity is a function of the nature of the antigen, the antigen dosage, the antigen form (soluble or particulated), the site of antigen administration, and the associa- (23). Thus, it seems that although both the nasal and oral mucosa may be sites for effective vaccination with LaAg, the antigen may be differentially presented at the two sites, as indicated by the partial tolerance and the active systemic immunity, respectively.…”

Discovery of Salmonella Virulence Factors Translocated via Outer Membrane Vesicles to Murine Macrophages

“…OMV not only disseminate toxins and enzymes into host cells to protect bacterial survival but also serve as bacterium-like decoys to neutralize the host immune responses and facilitate Gram-negative pathogens' immune evasion (10,71). OMV delivery of antigens has been a large area of investigation, as OMV could improve vaccines by delivery to the major histocompatibility complex (MHC) class I pathway while simultaneously providing pathogen-associated molecular patterns as adjuvants (2,4,62,73). Based on the accumulative observations of OMV in a variety of microorganisms, multiple biological functions of OMV, including virulence attributes and its biogenesis, including production mechanism and cargo selectivity have been reviewed recently (1,21,46).…”