2′-Fluoro-c-di-GMP as an oral vaccine adjuvant |
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| Authors: | Jia Li Rhonda Kuo Lee Wangxue Chen Hongbin Yan |
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| Institution: | Department of Chemistry, Brock University, 1812 Sir Isaac Brock Way, St. Catharines ON L2S 3A1 Canada.; Human Health and Therapeutics Research Center, National Research Council of Canada, 100 Sussex Dr, Ottawa ON K1A 0R6 Canada ; Department of Biological Sciences, Brock University, 1812 Sir Isaac Brock Way, St. Catharines ON L2S 3A1 Canada |
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| Abstract: | Bis-(3′–5′)-cyclic dimeric 2′-deoxy-2′-fluoroguanosine monophosphate (2′-F-c-di-GMP) was synthesized through the modified H-phosphonate chemistry. Oral immunization of C57BL/6 mice with Helicobacter pylori cell-free sonicate extract adjuvanted with 2′-F-c-di-GMP led to the production of antigen-specific antibodies in feces and sera, and lowered bacterial counts in the stomach upon post-vaccination infections in immunized mice. Similarly, oral vaccination of BALB/c mice with flagillin proteins from Clostridium difficile and Listeria monocytogenes adjuvanted with 2′-F-c-di-GMP led to production of antigen-specific antibodies both systemically and mucosally. The adjuvanticity of 2′-F-c-di-GMP is associated with the enhanced induction of interferon γ. These results demonstrated the excellent oral adjuvanticity of 2′-F-c-di-GMP.2′-F-c-di-GMP was synthesized through the modified H-phosphonate chemistry. 2′-F-c-di-GMP was found to be an effective mucosal vaccine adjuvant, both intranasally and orally. |
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