Use of fluorinated cyclic dinucleotides as oral vaccine adjuvants

Patent metadata

Field	Value
Publication number	US-10357560-B2
Application number	US-201816134417-A
Country	US
Kind code	B2
Filing date	Sep 18, 2018
Priority date	Nov 22, 2013
Publication date	Jul 23, 2019
Grant date	Jul 23, 2019

Abstract

Disclosed is the use of fluorinated cyclic dinucleotides and pharmaceutically acceptable salts thereof as an adjuvant for the preparation of an oral vaccine. Further disclosed is the use of fluorinated cyclic dinucleotides and pharmaceutically acceptable salts thereof for enhancing the immune response to an orally administered vaccine.

First claim

What is claimed is:

1. A method for preparing an oral vaccine, comprising admixing one or more non-replicating antigens with an adjuvant, wherein said adjuvant is a fluorinated cyclic dinucleotide having the following structure:

wherein A, C, A′ and C′ are independently selected from NH, O or S; X, Y, X′, and Y′ are independently selected from O or S; Z and Z′ are independently selected from O, S, NH or CH 2 ; and B 1 and B 2 are independently a purine selected from:

wherein Q is hydrogen or NH 2 ; nitrogen is optionally substituted with C 1 -C 6 alkyl or C 1 -C 6 acyl group; and R is O or S.

2. The method according to claim 1 , wherein the fluorinated cyclic dinucleotide is 2′-F-c-di-GMP having the following structure:

3. The method according to claim 1 , wherein the oral vaccine is an oral vaccine for the prevention or treatment of a gastrointestinal infection and wherein the gastrointestinal bacterial infection is a H. pylori infection, a C. difficile infection or a Listeria infection.

4. An oral vaccine comprising a fluorinated cyclic dinucleotide or a pharmaceutically acceptable salt thereof and a composition comprising H. pylori antigen, wherein said fluorinated cyclic dinucleotide has the following structure:

wherein A, C, A′ and C′ are independently selected from NH, O or S; X, Y, X′, and Y′ are independently selected from O or S; Z and Z′ are independently selected from O, S, NH or CH 2 ; and B 1 and B 2 are independently a purine selected from:

wherein Q is hydrogen or NH 2 ; nitrogen is optionally substituted with C 1 -C 6 alkyl or C 1 -C 6 acyl group; and R is O or S.

5. The oral vaccine according to claim 4 , wherein the fluorinated cyclic dinucleotide is 2′-F-c-di-GMP having the following structure:

6. The oral vaccine according to claim 4 , wherein the composition comprising H. pylori antigen comprises H. pylori cell free extract or one or more H. pylori specific peptides and/or proteins.

Assignees

• Brock Univ
• Nat Res Council Canada

Inventors

• Yan Hongbin
• Chen Wangxue
• Kuo Lee Rhonda

Classifications

• A61K2039/6037

  Bacterial toxins, e.g. diphteria toxoid [DT], tetanus toxoid [TT] · CPC title

• A61K2039/55561

  CpG containing adjuvants; Oligonucleotide containing adjuvants · CPC title

• A61K2039/543

  intranasal · CPC title

• A61K2039/542

  oral/gastrointestinal · CPC title

• A61K39/39 Primary

  characterised by the immunostimulating additives, e.g. chemical adjuvants · CPC title