Intranasal and Intramuscular Immunization with Outer Membrane Vesicles from Serogroup C Meningococci Induced Functional Antibodies and Immunologic Memory.

BACKGROUND

Immunization is the key to prevent invasive meningococcal disease (IMD), caused by . Outer membrane vesicles (OMVs) can be used as meningococcal antigens.

METHODS

Isogenic mice A/Sn (H2) were immunized with low antigenic doses of OMVs of an C:2a:P1.5 strain, via intranasal/intramuscular route, adjuvanted by cholera toxin subunit B (CTB) or via intramuscular route only, adjuvanted by aluminium hydroxide (AH). Mice were followed until old age and humoral and cellular responses were assessed by ELISA, Immunoblotting, Dot-blot, Serum-bactericidal assay, Immunohistochemistry and ELISpot.

RESULTS

OMV+CTB and OMV+AH groups presented statistically higher antibodies titers, which persisted until middle and old ages. IgG isotypes point to a Th2 type of response. Avidity indexes were considered high, regardless of adjuvant use, but only groups immunized with OMVs and adjuvants (OMV+CTB and OMV+AH) presented bactericidal activity. The antibodies recognized antigens of molecular weights attributed to porin and cross-reactivity proteins. Although the spleen of old mice did not present differences in immunohistochemistry marking of CD68+, CD4+, CD79+ and CD25+ cells, splenocytes of immune groups secreted IL-4 and IL-17 when stimulated with OMVs and meningococcal C polysaccharide.

CONCLUSION

We concluded that both adjuvants, CTB and AH, improved the immunogenicity of low doses of OMVs and contributed to a persistent immune response. Even though AH is well established in the vaccinology area, CTB seems to be a promising adjuvant candidate for meningococcal vaccines: it is suitable for mucosal delivery and supports a Th2 type of response. Therefore, OMVs are still a relevant vaccine platform.