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

Author(s)

Portilho, Amanda Izeli ; Correa, Victor Araujo ; Cirqueira, Cinthya dos Santos ; De Gaspari, Elizabeth

• Document type: Journal article
• Source: IMMUNOLOGICAL INVESTIGATIONS; v. 51, n. 7, p. 20-pg., 2022-08-12.

Abstract

Background Immunization is the key to prevent invasive meningococcal disease (IMD), caused by Neisseria meningitidis. Outer membrane vesicles (OMVs) can be used as meningococcal antigens. Methods Isogenic mice A/Sn (H2(a)) were immunized with low antigenic doses of OMVs of an N. meningitidis 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. (AU)

• FAPESP's process: 18/04202-0 - Study of the immunogenicity of outer membrane antigens of Neisseria meningitidis and interaction with cationic lipids: evaluation of new adjuvant for Neisseria meningitidis in different strains of elderly mice
• Grantee: Elizabeth Natal de Gaspari
• Support Opportunities: Regular Research Grants
• FAPESP's process: 12/15568-0 - Study of the immunogenicity of outer membrane antigens of Neisseria meningitidis and interaction with cationic lipids: evaluation of different immunization schedules in different strains of mice
• Grantee: Elizabeth Natal de Gaspari
• Support Opportunities: Regular Research Grants
• FAPESP's process: 19/02042-9 - Evaluation of response profiles of Th1 and Th2 in mice immunized with anionic and cationic lipids complexed the outer membrane vesicles of Neisseria meningitis b
• Grantee: Victor Araujo Correa
• Support Opportunities: Scholarships in Brazil - Master