期刊
VACCINE
卷 29, 期 32, 页码 5210-5220出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2011.05.026
关键词
Mucosal adjuvant; c-di-AMP; Intranasal administration; c-di-nucleotide
资金
- European Commission [044115, 228403]
New effective adjuvants are required to improve the performance of subunit vaccines. Here, we showed that bis-(3',5')-cyclic dimeric adenosine monophosphate (c-di-AMP), a second messenger molecule in bacteria and archaea, exerts strong adjuvant activities when delivered by mucosal route. In vitro studies showed that c-di-AMP was able to both stimulate pre-activated murine macrophages and promote the activation and maturation of dendritic cells of murine and human origin. Co-administration of c-di-AMP with beta-galactosidase (beta-Gal) by intranasal route to BALB/c mice resulted in the elicitation of significantly higher serum antigen-specific IgG titres than in controls. The induction of local immune responses was shown by the production of antigen-specific secretory IgA in different mucosal territories. In addition, strong cellular immune responses were observed against both the beta-Gal protein and a peptide encompassing its MHC class I-restricted epitope. The ratio of beta-Gal-specific antibodies and the secreted cytokine profiles by in vitro re-stimulated splenocytes suggested that a balanced Th1/Th2/Th17 response pattern is promoted by c-di-AMP. When C57BL/6 mice were immunized with OVA and c-di-AMP, vigorous in vivo CTL responses were also observed. These results indicated that c-di-AMP exhibits a high potential as adjuvant for the development of mucosal vaccines, in particular when cellular immunity is needed. (C) 2011 Elsevier Ltd. All rights reserved.
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