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

• Published in: RSC advances Vol. 9; no. 71; pp. 41481 - 41489
• Main Authors: Li, Jia, Lee, Rhonda Kuo, Chen, Wangxue, Yan, Hongbin
• Format: Journal Article
• Language: English
• Published: England Royal Society of Chemistry 16-12-2019; The Royal Society of Chemistry
• Subjects: Antibodies; Antigens; Chemical synthesis; Chemistry; Immunization; Interferon; Listeria; Organic chemistry; Phosphonates
• ISSN: 2046-2069; 2046-2069
• DOI: 10.1039/c9ra08310c

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.