Adjuvant comprising a glycoarchaeol and an immunostimulant
Provided is an adjuvant composition comprising a glycoarchaeol and at least one immunostimulant selected from a Toll-like receptor (TLR) agonist and a saponin. The glycoarchaeol and/or immunostimulant may be present as a pharmaceutically acceptable salt. The adjuvant composition may be comprised together with an antigen in an immunogenic composition, such as a vaccine composition, which may be for use to induce an immune response in a subject. Further provided is use of the immunogenic composition to induce an immune response in a subject, particularly an immune response that comprises both a cell-mediated response and a humoral response.
1 . An adjuvant composition comprising:
a glycoarchaeol or a pharmaceutically acceptable salt thereof, and
at least one immunostimulant selected from a Toll-like receptor (TLR) agonist or a pharmaceutically acceptable salt thereof,
wherein the TLR agonist is a TLR3 agonist or TLR9 agonist,
wherein the glycoarchaeol is a charged isoprenoid glycolipid comprising a sulfated saccharide group covalently linked to a free sn-1 hydroxyl group of a glycerol backbone of an archaeol core moiety via a beta linkage.
2 . The adjuvant composition of claim 1 , wherein the archaeol core moiety is 2,3-bis(((3,7,11)-3,7,11,15-tetramethylhexadecyl)oxy)propan-1-ol.
3 . The adjuvant composition of claim 1 , wherein the sulfated saccharide group is a sulfated disaccharide or trisaccharide.
4 . The adjuvant composition of claim 1 , wherein the sulfated saccharide group is 6′-sulfate-β-D-Galp-(1,4)-β-D-Glcp.
5 . The adjuvant composition of claim 1 , wherein the glycoarchaeol is 2,3 bis[(3,7,11)-3,7,11,15-tetramethylhexadecyloxy]propan-1-yl 4-O-(6-O-sulfo-β-D-galactopyranosyl)-β-D-glucopyranoside.
6 . The adjuvant composition of claim 1 , wherein the glycoarchaeol is of Formula I:
wherein n is 0 or 1;
R and R′ are independently hydrogen or hydroxyl; and
Y is hydrogen or a sulfate group, and at least one Y is a sulfate group.
7 . The adjuvant composition of claim 1 , wherein the glycoarchaeol is of the structure:
8 . The adjuvant composition of claim 1 , wherein the glycoarchaeol or the pharmaceutically acceptable salt thereof is comprised within an archaeosome.
9 . The adjuvant composition of claim 8 , wherein the archaeosome further comprises at least one additional lipid, and wherein the at least one additional lipid is a neutrally charged or uncharged glycolipid.
10 . The adjuvant composition of claim 9 , wherein the at least one additional lipid is a lactosylarchaeol, a rhamnosyl-lactosylarchaeol, a triglucosylarchaeol, or a combination of any two or more thereof.
11 . The adjuvant composition of claim 9 , wherein the mol % ratio of the glycoarchaeol or the pharmaceutically acceptable salt thereof to the at least one additional lipid is from 30:70 to about 50:50.
12 . The adjuvant composition of claim 1 , wherein the at least one immunostimulant is a TLR3 agonist, or a pharmaceutically acceptable salt thereof, wherein the TLR3 agonist is Poly(I:C) or a pharmaceutically acceptable salt thereof.
13 . An immunogenic composition comprising an antigen and the adjuvant composition of claim 1 .
14 . The immunogenic composition of claim 13 , wherein the antigen is a peptide, protein, or virus-like particle.
15 . A method of inducing an immune response in a subject, the method comprising administering to the subject the immunogenic composition of claim 14 .
16 . The method of claim 15 , wherein the immune response comprises a cell-mediated response and a humoral response, wherein the humoral response comprises an IgG response, and wherein the cell-mediated response comprises at least one of a CD4+ response, a CD8+ response, a cytotoxic response, and production of at least one cytokine.
17 . The adjuvant composition of claim 1 , wherein the at least one immunostimulant is a TLR9 agonist, or a pharmaceutically acceptable salt thereof, wherein the TLR9 agonist is an oligonucleotide comprising one or more CpG motifs.
18 . The immunogenic composition of claim 13 , which is a vaccine composition.
19 . The immunogenic composition of claim 18 , which is prepared by admixing the glycoarchaeol or the pharmaceutically acceptable salt thereof, the at least one immunostimulant, and the antigen.