The member of the cyclic di-nucleotide family bis-(3', 5')-cyclic dimeric inosine monophosphate exerts potent activity as mucosal adjuvant.
Here we demonstrated that bis-(3',5')-cyclic dimeric inosine monophosphate (c-di-IMP) exhibits potent adjuvant properties. BALB/c or C57BL/6 mice were immunized with the model antigens beta-galactosidase (beta-Gal) or Ovalbumin (OVA) alone or co-administered with c-di-IMP by the intranasal route. Animals receiving c-di-IMP showed significantly higher anti-beta-Gal or OVA immunoglobulin G titres (IgG) in sera than those vaccinated with beta-Gal or OVA alone. Furthermore, strong local immune responses were also detectable in different mucosal territories, as shown by the high levels of beta-Gal-specific secretory IgA (sIgA). The analysis of the antigen-specific IgG isotypes in sera, together with the profiles of the cytokines and chemokines secreted by lymphocytes from vaccinated animals showed that the use of c-di-IMP resulted in stimulation of a mixed T(H)1/T(H)2/T(H)17 response. Mucosal immunization of C57BL/6 mice with OVA using c-di-IMP as adjuvant also led to the stimulation of strong in vivo CTL responses (i.e., 60% of antigen-specific lysis) [corrected].Our results demonstrated that the novel compound c-di-IMP exhibits strong adjuvant properties when co-administered with an antigen by the mucosal route, thereby representing a promising candidate adjuvant for the development of mucosal vaccination strategies.
Libanova
Rimma
R
Department of Vaccinology and Applied Microbiology, Helmholtz Centre of Infection Research, Inhoffenstrasse 7, D-38124 Braunschweig, Germany.
Ebensen
Thomas
T
Department of Vaccinology and Applied Microbiology, Helmholtz Centre of Infection Research, Inhoffenstrasse 7, D-38124 Braunschweig, Germany. Electronic address: thomas.ebensen@helmholtz-hzi.de.
Schulze
Kai
K
Department of Vaccinology and Applied Microbiology, Helmholtz Centre of Infection Research, Inhoffenstrasse 7, D-38124 Braunschweig, Germany.
Bruhn
Daniela
D
Department of Vaccinology and Applied Microbiology, Helmholtz Centre of Infection Research, Inhoffenstrasse 7, D-38124 Braunschweig, Germany.
Nörder
Miriam
M
Department of Vaccinology and Applied Microbiology, Helmholtz Centre of Infection Research, Inhoffenstrasse 7, D-38124 Braunschweig, Germany.
Yevsa
Tetyana
T
Department of Vaccinology and Applied Microbiology, Helmholtz Centre of Infection Research, Inhoffenstrasse 7, D-38124 Braunschweig, Germany.
Morr
Michael
M
Department of Vaccinology and Applied Microbiology, Helmholtz Centre of Infection Research, Inhoffenstrasse 7, D-38124 Braunschweig, Germany.
Guzmán
Carlos A
CA
Department of Vaccinology and Applied Microbiology, Helmholtz Centre of Infection Research, Inhoffenstrasse 7, D-38124 Braunschweig, Germany.
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000281:Administration, Intranasal; D000818:Animals; D007289:Cyclic IMP / Q000008:administration & dosage*; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D005260:Female; D006801:Humans; D018928:Immunity, Mucosal; D007071:Immunoglobulin A, Secretory / Q000032:analysis; D007074:Immunoglobulin G / Q000097:blood; D008214:Lymphocytes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology*; D001616:beta-Galactosidase / Q000008:administration & dosage / Q000276:immunology*
D000276:Adjuvants, Immunologic; D016207:Cytokines; D007071:Immunoglobulin A, Secretory; D007074:Immunoglobulin G; D007289:Cyclic IMP; D010047:Ovalbumin; D001616:beta-Galactosidase