2'-Fluoro-c-di-GMP as an oral vaccine adjuvant

Jia Li; Rhonda Kuo Lee; Wangxue Chen; Hongbin Yan

doi:10.1039/c9ra08310c

2'-Fluoro-c-di-GMP as an oral vaccine adjuvant

RSC Adv. 2019 Dec 16;9(71):41481-41489. doi: 10.1039/c9ra08310c. eCollection 2019 Dec 13.

Authors

Jia Li¹, Rhonda Kuo Lee², Wangxue Chen^{2

3}, Hongbin Yan¹

Affiliations

¹ Department of Chemistry, Brock University 1812 Sir Isaac Brock Way St. Catharines ON L2S 3A1 Canada tyan@brocku.ca.
² Human Health and Therapeutics Research Center, National Research Council of Canada 100 Sussex Dr Ottawa ON K1A 0R6 Canada.
³ Department of Biological Sciences, Brock University 1812 Sir Isaac Brock Way St. Catharines ON L2S 3A1 Canada.

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.