Composition containing influenza vaccine
The present invention provides a composition comprising a universal influenza vaccine antigen and a vaccine adjuvant.
1. A composition comprising the following (1) and (2);
(1) a universal influenza vaccine antigen; and
(2) a vaccine adjuvant;
wherein the vaccine adjuvant is a substance which enhances the physiological activity of TLR7, which is selected from the group consisting of:
(4E,8E,12E,16E,20E)-N-{2-[{4-[(2-amino-4-{[(3S)-1-hydroxyhexan-3-yl]amino}-6-methylpyrimidin-5-yl)methyl]benzyl}(methyl)amino]ethyl}-4,8,12,17,21,25-hexamethylhexacosa-4,8,12,16,20,24-hexaenamide;
(4E,8E,12E,16E,20E)-1-(4-{4-[(2-amino-4-{[(2S)-1-hydroxypentan-2-yl]amino}-6-methylpyrimidin-5-yl)methyl]-3-methoxybenzyl}piperazin-1-yl)-4,8,12,17,21,25-hexamethylhexacosa-4,8,12,16,20,24-hexaen-1-one;
(4E,8E,12E,16E,20E)-1-(4-{4-[(2-amino-4-{[(2S)-1-hydroxypentan-2-yl]amino}-6-methylpyrimidin-5-yl)methyl]-3-methoxybenzoyl}piperazin-1-yl)-4,8,12,17,21,25-hexamethylhexacosa-4,8,12,16,20,24-hexaen-1-one;
4-[(2-amino-4-{[(2S)-1-hydroxypentan-2-yl]amino}-6-methylpyrimidin-5-yl)methyl]-N-(2-{[(4E,8E,12E,16E,20E)-4,8,12,17,21,25-hexamethylhexacosa-4,8,12,16,20,24-hexaenoyl]amino}ethyl)-3-methoxybenzamide; and
4-[(2-amino-4-{[(2S)-1-hydroxypentan-2-yl]amino}-6-methylpyrimidin-5-yl)methyl]-N-(2-{[(4E,8E,12E,16E,20E)-4,8,12,17,21,25-hexamethylhexacosa-4,8,12,16,20,24-hexaenoyl](methyl)amino}ethyl)-3-methoxybenzamide; or
a pharmaceutically acceptable salt thereof.
2. The composition according to claim 1 , wherein the universal influenza vaccine antigen is an influenza HA split vaccine antigen which produces an antibody that binds to a LAH of a HA stem region.
3. The composition according to claim 2 , wherein the influenza HA split vaccine antigen has a HA stem region exposed outside.
4. The composition according to claim 1 , wherein the universal influenza vaccine antigen is an influenza HA split vaccine antigen wherein the HA stem region, which is exposed outside, enhances the antigenicity of the LAH of the HA stem region, and the influenza HA split vaccine is capable of producing an antibody that binds to the LAH of the HA stem region.
5. The composition according to claim 1 , wherein the universal influenza vaccine antigen is produced by subjecting an influenza HA split vaccine to an acidic treatment.
6. The composition according to claim 1 , wherein the universal influenza vaccine antigen is produced by a production process including: subjecting an influenza HA split vaccine to an acidic treatment; and thereafter, subjecting the influenza HA split vaccine to a formalin treatment.
7. The composition according to claim 1 , wherein the substance which enhances the physiological activity of TLR7 is:
(4E,8E,12E,16E,20E)-N-{2-[{4-[(2-amino-4-{[(3S)-1-hydroxyhexan-3-yl]amino}-6-methylpyrimidin-5-yl)methyl]benzyl}(methyl)amino]ethyl}-4,8,12,17,21,25-hexamethylhexacosa-4,8,12,16,20,24-hexaenamide; or
4-[(2-amino-4-{[(2S)-1-hydroxypentan-2-yl]amino}-6-methylpyrimidin-5-yl)methyl]-N-(2-{[(4E,8E,12E,16E,20E)-4,8,12,17,21,25-hexamethylhexacosa-4,8,12,16,20,24-hexaenoyl]amino}ethyl)-3-methoxybenzamide; or
a pharmaceutically acceptable salt thereof.
8. An influenza vaccine comprising the composition according to claim 1 .
9. A kit comprising a universal influenza vaccine antigen, and a vaccine adjuvant;
wherein the vaccine adjuvant is a substance which enhances the physiological activity of TLR7, which is selected from the group consisting of:
(4E,8E,12E,16E,20E)-N-{2-[{4-[(2-amino-4-{[(3S)-1-hydroxyhexan-3-yl]amino}-6-methylpyrimidin-5-yl)methyl]benzyl}(methyl)amino]ethyl}-4,8,12,17,21,25-hexamethylhexacosa-4,8,12,16,20,24-hexaenamide;
(4E,8E,12E,16E,20E)-1-(4-{4-[(2-amino-4-{[(2S)-1-hydroxypentan-2-yl]amino}-6-methylpyrimidin-5-yl)methyl]-3-methoxybenzyl}piperazin-1-yl)-4,8,12,17,21,25-hexamethylhexacosa-4,8,12,16,20,24-hexaen-1-one;
(4E,8E,12E,16E,20E)-1-(4-{4-[(2-amino-4-{[(2S)-1-hydroxypentan-2-yl]amino}-6-methylpyrimidin-5-yl)methyl]-3-methoxybenzoyl}piperazin-1-yl)-4,8,12,17,21,25-hexamethylhexacosa-4,8,12,16,20,24-hexaen-1-one;
4-[(2-amino-4-{[(2S)-1-hydroxypentan-2-yl]amino}-6-methylpyrimidin-5-yl)methyl]-N-(2-{[(4E,8E,12E,16E,20E)-4,8,12,17,21,25-hexamethylhexacosa-4,8,12,16,20,24-hexaenoyl]amino}ethyl)-3-methoxybenzamide; and
4-[(2-amino-4-{[(2S)-1-hydroxypentan-2-yl]amino}-6-methylpyrimidin-5-yl)methyl]-N-(2-{[(4E,8E,12E,16E,20E)-4,8,12,17,21,25-hexamethylhexacosa-4,8,12,16,20,24-hexaenoyl](methyl)amino}ethyl)-3-methoxybenzamide; or
a pharmaceutically acceptable salt thereof.
10. The composition according to claim 1 , wherein the universal influenza vaccine antigen is produced by subjecting an influenza HA split vaccine which has not undergone a formalin treatment to an acidic treatment.
11. The composition according to claim 1 , wherein the universal influenza vaccine antigen is produced by subjecting an influenza HA split vaccine of a single HA subtype to an acidic treatment.
12. The composition of according to claim 1 , wherein the universal influenza vaccine antigen is a vaccine antigen comprising two or more kinds of influenza HA split vaccine antigens each of which is produced by subjecting an influenza HA split vaccine of a single HA subtype to an acidic treatment.
13. The composition according to claim 1 , wherein the substance which enhances the physiological activity of TLR7 is:
(4E,8E,12E,16E,20E)-N-{2-[{4-[(2-amino-4-{[(3S)-1-hydroxyhexan-3-yl]amino}-6-methylpyrimidin-5-yl)methyl]benzyl}(methyl)amino]ethyl}-4,8,12,17,21,25-hexamethylhexacosa-4,8,12,16,20,24-hexaenamide; or
a pharmaceutically acceptable salt thereof.
14. The composition according to claim 1 , wherein the universal influenza vaccine antigen is an influenza HA split vaccine antigen which produces an antibody that binds to a LAH of a HA stem region, and the substance which enhances the physiological activity of TLR7 is (4E,8E,12E,16E,20E)-N-{2-[{4-[(2-amino-4-{[(3S)-1-hydroxyhexan-3-yl]amino}-6-methylpyrimidin-5-yl)methyl]benzyl}(methyl)amino]ethyl}-4,8,12,17,21,25-hexamethylhexacosa-4,8,12,16,20,24-hexaenamide or a pharmaceutically acceptable salt thereof.
15. The composition according to claim 1 , wherein the universal influenza vaccine antigen is produced by subjecting an influenza HA split vaccine to an acidic treatment, and the substance which enhances the physiological activity of TLR7 is (4E,8E,12E,16E,20E)-N-{2-[{4-[(2-amino-4-{[(3S)-1-hydroxyhexan-3-yl]amino}-6-methylpyrimidin-5-yl)methyl]benzyl}(methyl)amino]ethyl}-4,8,12,17,21,25-hexamethylhexacosa-4,8,12,16,20,24-hexaenamide or a pharmaceutically acceptable salt thereof.
16. The influenza vaccine according to claim 8 , wherein the universal influenza vaccine antigen is an influenza HA split vaccine antigen which produces an antibody that binds to a LAH of a HA stem region, and the substance which enhances the physiological activity of TLR7 is (4E,8E,12E,16E,20E)-N-{2-[{4-[(2-amino-4-{[(3S)-1-hydroxyhexan-3-yl]amino}-6-methylpyrimidin-5-yl)methyl]benzyl}(methyl)amino]ethyl}-4,8,12,17,21,25-hexamethylhexacosa-4,8,12,16,20,24-hexaenamide or a pharmaceutically acceptable salt thereof.
17. The influenza vaccine according to claim 8 , wherein the universal influenza vaccine antigen is produced by subjecting an influenza HA split vaccine to an acidic treatment, and the substance which enhances the physiological activity of TLR7 is (4E,8E,12E,16E,20E)-N-{2-[{4-[(2-amino-4-{[(3S)-1-hydroxyhexan-3-yl]amino}-6-methylpyrimidin-5-yl)methyl]benzyl}(methyl)amino]ethyl}-4,8,12,17,21,25-hexamethylhexacosa-4,8,12,16,20,24-hexaenamide or a pharmaceutically acceptable salt thereof.
18. The kit according to claim 9 , wherein the universal influenza vaccine antigen is an influenza HA split vaccine antigen which produces an antibody that binds to a LAH of a HA stem region, and the substance which enhances the physiological activity of TLR7 is (4E,8E,12E,16E,20E)-N-{2-[{4-[(2-amino-4-{[(3S)-1-hydroxyhexan-3-yl]amino}-6-methylpyrimidin-5-yl)methyl]benzyl}(methyl)amino]ethyl}-4,8,12,17,21,25-hexamethylhexacosa-4,8,12,16,20,24-hexaenamide or a pharmaceutically acceptable salt thereof.
19. The kit according to claim 9 , wherein the universal influenza vaccine antigen is produced by subjecting an influenza HA split vaccine to an acidic treatment, and the substance which enhances the physiological activity of TLR7 is (4E,8E,12E,16E,20E)-N-{2-[{4-[(2-amino-4-{[(3S)-1-hydroxyhexan-3-yl]amino}-6-methylpyrimidin-5-yl)methyl]benzyl}(methyl)amino]ethyl}-4,8,12,17,21,25-hexamethylhexacosa-4,8,12,16,20,24-hexaenamide or a pharmaceutically acceptable salt thereof.