The member of the cyclic di-nucleotide family bis-(3 ', 5 ')-cyclic dimeric inosine monophosphate exerts potent activity as mucosal adjuvant

作者：Libanova Rimma; Ebensen Thomas^*; Schulze Kai; Bruhn Daniela; Noerder Miriam; Yevsa Tetyana; Morr Michael; Guzman Carlos A

来源：Vaccine, 2010, 28(10): 2249-2258.

DOI：10.1016/j.vaccine.2009.12.045

• Adjuvant
• c-di-IMP
• Immune modulation
• Mucosal adjuvant
• Vaccine

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 P-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 (slgA). 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 both humoral and cellular (i.e., 60% of antigen-specific lysis by in vivo CTL) responses. 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.

• 出版日期2010-3-2