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

Abstract:

: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.

journal_name

Vaccine

journal_title

Vaccine

authors

Libanova R,Ebensen T,Schulze K,Bruhn D,Nörder M,Yevsa T,Morr M,Guzmán CA

doi

10.1016/j.vaccine.2009.12.045

subject

Has Abstract

pub_date

2010-03-02 00:00:00

pages

2249-2258

issue

10

eissn

0264-410X

issn

1873-2518

pii

S0264-410X(09)01949-5

journal_volume

28

pub_type

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