Vaccine composition containing synthetic adjuvant
Compositions and methods, including vaccines and pharmaceutical compositions for inducing or enhancing an immune response are disclosed based on the discovery of useful immunological adjuvant properties in a synthetic, glucopyranosyl lipid adjuvant (GLA) that is provided in substantially homogeneous form. Chemically defined, synthetic GLA offers a consistent vaccine component from lot to lot without the fluctuations in contaminants or activity that compromise natural-product adjuvants. Also provided are vaccines and pharmaceutical compositions that include GLA and one or more of an antigen, a Toll-like receptor (TLR) agonist, a co-adjuvant and a carrier such as a pharmaceutical carrier.
1. A vaccine composition comprising:
(a) one or more antigens, or at least one nucleic acid sequence encoding a polypeptide antigen;
(b) a pharmaceutically acceptable carrier or excipient, and
(c) a lipid adjuvant of the formula:
wherein:
R 1 , R 3 , R 5 and R 6 are undecyl; and
R 2 and R 4 are tridecyl;
or a pharmaceutically acceptable salt thereof; and
wherein the one or more antigens, or at least one nucleic acid sequence encoding a polypeptide antigen is from an influenza virus.
2. The composition of claim 1 wherein the antigen is selected from the group consisting of whole live influenza virus, inactivated influenza virus, split influenza virus, whole influenza virus virosomes; influenza virus HA protein, influenza virus NP protein, influenza virus NA protein, and influenza virus M proteins, or combinations thereof.
3. The composition of claim 2 wherein the influenza virus is a pandemic influenza virus.
4. The composition of claim 1 wherein the adjuvant is synthetic.
5. The composition of claim 1 wherein the adjuvant is at least 80% pure, based on the total weight of lipid adjuvants in the composition.
6. The composition of claim 1 wherein the adjuvant is at least 95% pure, based on the total weight of lipid adjuvants in the composition.
7. The composition of claim 1 which has been sterile filtered.
8. The composition of claim 1 comprising a plurality of antigens.
9. The composition of claim 1 comprising a plurality of influenza virus antigens.
10. The composition of claim 1 , further comprising at least one additional component selected from the group consisting of:
a toll-like receptor (TLR) agonist;
a saponin or saponin mimetic;
a co-adjuvant; and
a carrier that comprises at least one of an oil and an immunostimulatory complex.
11. The composition of claim 10 wherein:
(i) the TLR agonist, when present, is selected from the group consisting of lipopolysaccharide, peptidoglycan, poly I:C, CpG, 3M003, flagellin, Leishmania homolog of eukaryotic ribosomal elongation and initiation factor 4a (LeIF) and an imidazoquinoline immune response modifier; and
(ii) the co-adjuvant, when present, is selected from the group consisting of alum, a cytokine, a detergent, a block copolymer and a biodegradable polymer; and
(iii) the carrier, when present, comprises a carrier that is selected from the group consisting of calcium phosphate, a liposome, and a microparticle.
12. The composition of claim 1 wherein the composition is in the form of an oil-in water emulsion or water-in-oil emulsion.
13. The composition of claim 1 wherein the composition is an aqueous formulation.