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

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

doi:10.1039/c9ra08310c

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.

Highlights

In the last decade or so, 30,50-cyclic diguanylic acid (c-di-GMP) has been recognized as a potent immunostimulator and a useful mucosal adjuvant in a number of models.[1,2] It was previously demonstrated by us that intranasal administration of c-di-GMP prior to bacterial challenges provides mice with protection against Acinetobacter baumannii infection by chemokine induction and enhanced neutrophil recruitment.[3]
We previously demonstrated the synthesis of c-di-GMP via the modi ed H-phosphonate chemistry.[10,11]
These results demonstrated that 20-Fc-di-GMP is a potent mucosal adjuvant when administered by intranasal route, and that 20-F-c-di-GMP induces a potent, protective immunity against i.n. challenge with S. pneumoniae when co-administered with the pneumococcal surface adhesion A (PsaA) antigen via i.n. route

Summary

Introduction

In the last decade or so, 30,50-cyclic diguanylic acid (c-di-GMP) has been recognized as a potent immunostimulator and a useful mucosal adjuvant in a number of models.[1,2] It was previously demonstrated by us that intranasal administration of c-di-GMP prior to bacterial challenges provides mice with protection against Acinetobacter baumannii infection by chemokine induction and enhanced neutrophil recruitment.[3]. We report that oral immunization of C57BL/6 mice with H. pylori cell-free sonicate extract (HPCE) adjuvanted with 20-F-c-di-GMP led to the production of antigen-speci c aDepartment of Chemistry, Brock University, 1812 Sir Isaac Brock Way, St. Catharines, ON L2S 3A1, Canada. Oral immunization with 20-F-c-di-GMP-adjuvanted vaccine induces strong antigen-speci c antibody responses in the serum and at multiple mucosal sites

Results

Conclusion