Immunogenic composition in emulsion form comprising two dispersed phases, one comprising an antigen and the other comprising an immunostimulating agent

Patent metadata

Field	Value
Publication number	US-9968673-B2
Application number	US-201514944825-A
Country	US
Kind code	B2
Filing date	Nov 18, 2015
Priority date	Feb 26, 2013
Publication date	May 15, 2018
Grant date	May 15, 2018

Abstract

The application relates to an immunogenic composition comprising a continuous aqueous phase and at least two dispersed phases 1 and 2 as droplets, wherein the dispersed phase 1 comprises a surfactant 1 bearing an antigen and the dispersed phase 2 comprises an immunostimulating agent 2, to its preparation method and its uses, notably for producing antibodies, as a drug, as a vaccine or in an immunization method.

First claim

What is claimed is:

1. An immunogenic composition comprising a continuous aqueous phase and at least two dispersed phases 1 and 2 as droplets wherein:
the dispersed phase 1 comprises:
an amphiphilic lipid 1,
a solubilizing lipid 1 comprising at least one fatty acid glyceride,
a co-surfactant 1 comprising at least one chain consisting of alkylene oxide units,
a surfactant 1 bearing an antigen of the following formula (I′):

wherein:
R 2 represents a linear hydrocarbon chain comprising from 7 to 23 carbon atoms,
A 2 represents O or NH,
n represents an integer from 3 to 500, and
Ag represents an antigen,

wherein the molar ratio of the surfactant 1 bearing an antigen of formula (I′) over the sum of the co-surfactant 1 and of the surfactant 1 bearing an antigen of formula (I′) is from 0.01% to 5%, and
wherein the dispersed phase 2 comprises:

an amphiphilic lipid 2,
a solubilizing lipid 2 comprising at least one fatty acid glyceride,
a co-surfactant 2 comprising at least one chain consisting of alkylene oxide units, and
an immunostimulating agent 2,
with the proviso that the dispersed phase 2 is free of surfactant bearing an antigen of formula (I′).

2. The immunogenic composition according to claim 1 , wherein:
the amphiphilic lipid 1 and/or the amphiphilic lipid 2 is(are) a phospholipid, and/or
the solubilizing lipid 1 and/or the solubilizing lipid 2 consist(s) of a mixture of saturated fatty acid glycerides including at least 10% by weight of C 12 fatty acids, at least 5% by weight of C 14 fatty acids, at least 5% by weight of C 16 fatty acids and at least 5% by weight of C18 fatty acids, and/or
the co-surfactant 1 and/or the co-surfactant 2 is(are) selected from polyethyleneglycol/phosphatidyl-ethanolamine conjugate compounds, fatty acid and polyethyleneglycol ethers, fatty acid and polyethyleneglycol esters and block copolymers of ethylene oxide and propylene oxide, and the polyalkoxylated chain of the co-surfactant 1 and/or the co-surfactant 2 comprise(s) from 10 to 200 ethylene oxide/propylene oxide units.

3. The immunogenic composition according to claim 1 , wherein the immunostimulating agent 2 is a “Toll-like receptor” (TLR) ligand.

4. The immunogenic composition according to claim 1 , wherein:
the dispersed phase 1 comprises a biological targeting ligand 1 either grafted or not on the co-surfactant 1, and/or the dispersed phase 2 comprises a biological targeting ligand 2 either grafted or not on the co-surfactant 2, and/or
the dispersed phase 1 comprises an agent 1 of interest selected from an optical agent or a physical agent, and/or the dispersed phase 2 comprises an agent 2 of interest selected from an optical agent and a physical agent.

5. The immunogenic composition according to claim 1 , wherein the dispersed phase 2 comprises:
oligodeoxynucleotide CpG as immunostimulating agent 2,
a co-surfactant 2 comprising at least a poly (ethylene oxide) chain comprising at least 25 ethylene oxide units,
a cationic surfactant 2, and
optionally a helper lipid 2.

6. The immunogenic composition according to claim 1 , wherein the dispersed phase 2 comprises:
from 0.1 to 10% by weight of monophosphoryl lipid A as immunostimulating agent 2 with respect to the weight of dispersed phase 2, and
from 0.1 to 40% by weight of co-surfactant 2 with respect to the weight of dispersed phase 2.

7. A drug or a vaccine comprising the immunogenic composition according to claim 1 .

8. The immunogenic composition according to claim 3 , wherein the immunostimulating agent 2 is chosen from monophosphoryl lipid A (MPLA), oligodeoxynucleotide (ODN) CpG, imiquimod and resiquimod.

9. The immunogenic composition according to claim 1 , wherein A 2 represents NH.

Assignees

• Commissariat Energie Atomique
• Inst Nat Sante Rech Med
• Commissariat Energie Atomique

Inventors

• Navarro Y Garcia Fabrice
• Bayon Emilie
• Marche Patrice
• Courant Thomas

Classifications

• C07K2317/10

  characterized by their source of isolation or production · CPC title

• A61K2039/55561

  CpG containing adjuvants; Oligonucleotide containing adjuvants · CPC title

• C07K2317/34

  Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues · CPC title

• A61K2039/55572

  Lipopolysaccharides; Lipid A; Monophosphoryl lipid A · CPC title

• C07K16/18

  against material from animals or humans · CPC title