Adjuvant
OwnerRalph P. Braun, Lindy Thomsen +2inventors
InventorsRalph P. Braun, Lindy Thomsen, Catherine Van-Wely, Peter Ertl
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Abstract
The present invention relates to the fields of vaccines, vaccine adjuvants, molecular biology and immunology, and generally adjuvants and nucleic acid immunization techniques. More specifically, the invention relates to certain adjuvant compositions, and to vaccine and/or nucleic acid immunization strategies employing such compositions. The invention in particular relates to DNA vaccines that are useful in the prophylaxis and treatment of HIV infections, more particularly when administered by particle mediated delivery.
Claims27
Method enhancing in an individual an immune response generated by a nucleic acid vaccine, said method comprising administering a compound which is an imidazoquinoline amine, imidazopyridine amine, 6,7-fused cycloalkylimidazopyridine amine, 1,2-bridged imidazoquinoline amine, thiazolo- or oxazolo-quinolinamine or pyridinamines, imidazonaphthyridine or tetrahydroimidazonaphthyridine amine,
- wherein the compound is administered topically or transdermally to the individual 12 to 36 hours after the nucleic acid vaccine is administered, and wherein the nucleic acid vaccine comprises a nucleotide sequence that encodes an HIV-1 gag protein or fragment containing a gag epitope thereof and a second HIV antigen or a fragment encoding an epitope of said second HIV antigen, operably linked to a heterologous promoter.
Method according to any one of the preceding claims wherein the nucleic acid vaccine is administered topically or transdermally.
Method according to any one of the preceding claims wherein the nucleic acid vaccine is administered in the form of particles.
Method according to any one of the preceding claims wherein the compound is administered in the form of particles.
Method according to any one of the preceding claims in which the compound is administered in the form of a cream.
Method according to any one of the preceding claims wherein the administration of the antigen or polynucleotide is repeated to provide a prime and booster administration.
Method according to any one of the preceding claims wherein the second antigen is selected from the group consisting of:
- Nef, RT or a fragment containing an epitope of Nef or RT.
Method according to any one of the preceding claims wherein the gag protein comprises p17.
Method according to any one of the preceding claims wherein the gag sequence is codon optimised to resemble the codon usage in a highly expressed human gene.
Method according to any one of the preceding claims wherein the nucleotide sequence encodes a Nef protein or epitope thereof.
Method according to any one of the preceding claims wherein the nucleotide sequence is selected from the group
- Gag (p17,p24) Nef truncate
- Gag (p17,p24) (codon optimised) Nef (truncate)
- Gag (p17,p24) RT Nef (truncate)
- Gag (p17,p24) codon optimised RT Nef (truncate)
- Gag (p17,p24) codon optimised RT codon optimised Nef truncate
Method according to any one of the preceding claims wherein the heterologous promoter is the minimal promoter from HCMV IE gene.
Method according to any one of the preceding claims wherein the nucleic acid sequence is in the form of a double stranded DNA plasmid.
Method according to any one of the preceding claims wherein the nucleic acid sequence encodes Gag (or a fragment thereof which comprises au epitope) and RT (or a fragment thereof which comprises an epitope) and Nef (or a fragment thereof which comprises an epitope) in any order.
Method according to any one of the preceding claims wherein at least one of the proteins which is encoded by the nucleic acid is a fusion protein.
Use of compound which is an imidazoquinoline amine, imidazopyridine amine, 6,7-fused cycloalkylimidazopyridine amine, 1,2-bridged imidazoquinoline amine, thiazolo- and oxazolo-quinolinamine or pyridinamine, imidazonaphthyridine or tetrahydroimidazonaphthyridine amine in the manufacture of a medicament to enhance an immune response to an antigen, wherein the compound is administered topically or transdermally to the individual 12 to 36 hours after a nucleic acid vaccine is administered, and wherein the nucleic acid vaccine comprises a nucleotide sequence that encodes an HIV-1 gag protein or fragment containing a gag epitope thereof and a second HIV antigen or a fragment encoding an epitope of said second HIV antigen, operably linked to a heterologous promoter.
Use of a nucleotide sequence that encodes an HIV-1 gag protein or fragment containing a gag epitope thereof and a second HIV antigen or a fragment encoding an epitope of said second HIV antigen, operably linked to a heterologous promoter in the manufacture of a nucleic acid vaccine, wherein 12 to 36 hours subsequent to the administration of the nucleic acid vaccine to an individual a compound which is an imidazoquinoline amine, imidazopyridine amine, 6,7-fused cycloalkylimidazopyridine amine, 1,2-bridged imidazoquinoline amine, thiazolo- and oxazolo-quinolinamine or pyridinamine, imidazonaphthyridine or tetrahydroimidazonaphthyridine amine is administered topically or transdermally to the individual.
A product containing (i) a nucleic acid vaccine that comprises a nucleotide sequence that encodes an HIV-1 gag protein or fragment containing a gag epitope thereof and a second HIV antigen or a fragment encoding an epitope of said second HIV antigen, operably lined to a heterologous promoter, and (ii) a compound which is an imidazoquinoline amine, imidazopyridine amine, 6,7-fused cycloalkylimidazopyridine amine, 1,2-bridged imidazoquinoline amine, thiazolo- and oxazolo-quinolinamine or pyridinamine, imidazonaphthyridine or tetrahydroimidazonaphthyridine amine for sequential use, wherein the compound is administered topically or transdermally 12 to 36 hours after administration of the nucleic acid vaccine.
Dependencies are inferred from the claim text.