Use and preparation of glycolipids as adjuvants in vaccines

Patent metadata

Field	Value
Publication number	US-10722574-B2
Application number	US-201816007685-A
Country	US
Kind code	B2
Filing date	Jun 13, 2018
Priority date	Jun 10, 2013
Publication date	Jul 28, 2020
Grant date	Jul 28, 2020

Abstract

The present invention relates to beta-glycolipid derivatives, their preparation and use as adjuvants in vaccines, as being suitable for being co-administered with antigens for vaccine prophylaxis and therapy. In certain embodiments, the beta-glycolipid derivatives of the invention also in their salified or complex form, are suitable for being co-administered with antigens for both therapeutic and prophylactic purposes or for vaccine prophylaxis and therapy.

First claim

The invention claimed is:

1. A method for modulating the immune response following the administration of an antigen or a vaccine to a subject in need thereof, said method comprising the administration of a vaccine adjuvant composition, said vaccine adjuvant composition comprising at least one beta-glycolipid derivative of formula (I):

or a salt or a metal complex thereof,
wherein
the acetalic bond of the anomeric carbon has β (beta) configuration,
A 1 and A 2 are, independently of each other, saturated or monounsaturated linear or branched C 1 -C 30 alkyl, or are an acyl —(CO)R 1 and —(CO)R 2 respectively where R 1 and R 2 are, independently of each other, saturated or monounsaturated linear or branched C 1 -C 29 alkyl, and X is a sulphonic (—SO 3 H), sulphuric (—OSO 3 H), phosphoric (—OPO 3 H 2 ), or phosphonic (—PO 3 H 2 ) group,
wherein said at least one beta-glycolipid derivative of formula (I) stimulates the immune system by activating antigen-presenting cells.

2. The method of claim 1 , wherein said antigen-presenting cells are dendritic cells.

3. The method of claim 1 , wherein the vaccine adjuvant composition is co-administered with an antigen against which the subject in need thereof has to be immunized.

4. The method of claim 1 , wherein, in the beta-glycolipid derivative, A 1 and A 2 or R 1 and R 2 are, independently of each other, saturated or monounsaturated linear C 6 -C 24 alkyl.

5. The method of claim 1 , wherein, in the beta-glycolipid derivative, A 1 and A 2 or R 1 and R 2 are, independently of each other, moieties of lauric acid, myristic acid, palmitic acid, stearic acid, arachidic acid, behenic acid or lignoceric acid.

6. The method of claim 1 , wherein, in the beta-glycolipid derivative, A 1 and A 2 or R 1 and R 2 are, independently of each other, saturated or monounsaturated linear C 14 -C 18 alkyl.

7. The method of claim 1 , wherein, in the beta-glycolipid derivative, A 1 and A 2 are acyl —(CO)R 1 and acyl —(CO)R 2 respectively, where R 1 and R 2 are, independently of each other, a moiety of pentadecanoic acid, palmitic acid, heptadecanoic acid, or stearic acid.

8. The method of claim 1 , wherein the beta-glycolipid derivative of formula (I) is in the form of a salt thereof, wherein X is a —SO 3 - , —OSO 3 - , —OPO 3 2- , —PO 3 2- , wherein the metal ion is from the alkali or alkaline-earth metal group.

9. The method of claim 1 , wherein, in the beta-glycolipid derivative, X is —SO 3 H, —SO 3 Na, or —SO 3 K.

10. The method of claim 1 , wherein the beta-glycolipid derivative of formula (I) is in the form of a complex thereof with aluminium.

11. The method of claim 1 , wherein said beta-glycolipid derivative is sodium or potassium salt of 1,2-diacyl-3-[1′β-(6-sulpho)-quinovosyl]-glycerol.

12. The method of claim 1 , wherein said beta-glycolipid derivative is 1,2-distearoyl -3-[1′β-(6-sulpho)-quinovosyl]-glycerol.

13. The method of claim 1 , wherein said beta-glycolipid derivative is 1,2-dipalmitoyl -3-[1′β-(6-sulpho)-quinovosyl]-glycerol.

14. The method of claim 1 , wherein said beta-glycolipid derivative is 1-palmitoyl-2-stearoyl-3-[1′β-(6-sulpho)-quinovosyl]-glycerol or 1-stearoyl -2-palmitoyl-3-[1′β-(6-sulpho)-quinovosyl]-glycerol.

15. The method of claim 1 , wherein the vaccine adjuvant composition comprises at least one beta-glycolipid derivative of formula (I), a pharmaceutically acceptable salt or metal complex thereof.

16. The method of claim 3 , wherein the vaccine adjuvant composition and the antigen are provided in the form of a product or kit containing them, for their simultaneous, separate or sequential administration.

Assignees

• Consiglio Nazionale Ricerche

Inventors

• Fontana Angelo
• Manzo Emiliano
• Cutignano Adele
• De Palma Raffaele

Classifications

• A61K39/39 Primary

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

• C07H13/06

  Fatty acids · CPC title