RU2011146016A - Композиции для иммунизации против staphylococcus aureus - Google Patents
Композиции для иммунизации против staphylococcus aureus Download PDFInfo
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- 239000000203 mixture Substances 0.000 title claims abstract 18
- 241000191967 Staphylococcus aureus Species 0.000 title 1
- 230000003053 immunization Effects 0.000 title 1
- 238000002649 immunization Methods 0.000 title 1
- 239000000427 antigen Substances 0.000 claims abstract 308
- 102000036639 antigens Human genes 0.000 claims abstract 308
- 108091007433 antigens Proteins 0.000 claims abstract 308
- 101150024289 hly gene Proteins 0.000 claims abstract 8
- 101150085107 clfA gene Proteins 0.000 claims abstract 6
- 101150016690 esxA gene Proteins 0.000 claims abstract 6
- 101150079015 esxB gene Proteins 0.000 claims abstract 6
- 230000002163 immunogen Effects 0.000 claims abstract 5
- 101100455927 Mus musculus Maea gene Proteins 0.000 claims abstract 4
- 101100041727 Staphylococcus aureus (strain NCTC 8325 / PS 47) sasF gene Proteins 0.000 claims abstract 4
- 101150035844 clfB gene Proteins 0.000 claims abstract 4
- 101150018857 emp gene Proteins 0.000 claims abstract 4
- 101150026034 esxC gene Proteins 0.000 claims abstract 4
- 101150116335 isdA gene Proteins 0.000 claims abstract 4
- 101150057984 isdB gene Proteins 0.000 claims abstract 4
- 101150003115 isdC gene Proteins 0.000 claims abstract 4
- 101150064504 sdrC gene Proteins 0.000 claims abstract 4
- 101150009625 sdrD gene Proteins 0.000 claims abstract 4
- 101100523490 Dictyostelium discoideum rab8A gene Proteins 0.000 claims abstract 3
- 101100411591 Dictyostelium discoideum rab8B gene Proteins 0.000 claims abstract 3
- 101100084025 Mus musculus Alpg gene Proteins 0.000 claims abstract 3
- ZAWXOCUFQSQDJS-UHFFFAOYSA-N Ochromycinone Natural products O=C1C2=C(O)C=CC=C2C(=O)C2=C1C=CC1=C2C(=O)CC(C)C1 ZAWXOCUFQSQDJS-UHFFFAOYSA-N 0.000 claims abstract 3
- 240000005499 Sasa Species 0.000 claims abstract 3
- 101100344096 Staphylococcus aureus (strain MSSA476) lukDv gene Proteins 0.000 claims abstract 3
- 101100344097 Staphylococcus aureus lukD gene Proteins 0.000 claims abstract 3
- 101100344099 Staphylococcus aureus lukE gene Proteins 0.000 claims abstract 3
- 101100344100 Staphylococcus aureus lukF gene Proteins 0.000 claims abstract 3
- 101100182659 Staphylococcus aureus lukS gene Proteins 0.000 claims abstract 3
- 101150009986 ebhA gene Proteins 0.000 claims abstract 3
- 101150032154 ebpS gene Proteins 0.000 claims abstract 3
- 101150030247 fib gene Proteins 0.000 claims abstract 3
- 101150104841 hlgB gene Proteins 0.000 claims abstract 3
- 101150057138 hlgC gene Proteins 0.000 claims abstract 3
- 101150014673 isdG gene Proteins 0.000 claims abstract 3
- 101150074910 isdH gene Proteins 0.000 claims abstract 3
- 101150020318 isdI gene Proteins 0.000 claims abstract 3
- 101150009569 sasA gene Proteins 0.000 claims abstract 3
- 101150078985 sraP gene Proteins 0.000 claims abstract 3
- 229920001184 polypeptide Polymers 0.000 claims 13
- 102000004196 processed proteins & peptides Human genes 0.000 claims 13
- 108090000765 processed proteins & peptides Proteins 0.000 claims 13
- 125000003275 alpha amino acid group Chemical group 0.000 claims 8
- 150000001413 amino acids Chemical class 0.000 claims 7
- 239000012634 fragment Substances 0.000 claims 5
- 102000014914 Carrier Proteins Human genes 0.000 claims 4
- 108010078791 Carrier Proteins Proteins 0.000 claims 4
- 229920002444 Exopolysaccharide Polymers 0.000 claims 2
- 241000124008 Mammalia Species 0.000 claims 2
- 239000002671 adjuvant Substances 0.000 claims 2
- 150000004676 glycans Chemical class 0.000 claims 2
- 229920001282 polysaccharide Polymers 0.000 claims 2
- 239000005017 polysaccharide Substances 0.000 claims 2
- 102000004169 proteins and genes Human genes 0.000 claims 2
- 108090000623 proteins and genes Proteins 0.000 claims 2
- 125000001433 C-terminal amino-acid group Chemical group 0.000 claims 1
- 125000001429 N-terminal alpha-amino-acid group Chemical group 0.000 claims 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 claims 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 1
- -1 coA Proteins 0.000 claims 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 claims 1
- 230000028993 immune response Effects 0.000 claims 1
- 230000001939 inductive effect Effects 0.000 claims 1
- 102000039446 nucleic acids Human genes 0.000 claims 1
- 108020004707 nucleic acids Proteins 0.000 claims 1
- 150000007523 nucleic acids Chemical class 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/02—Bacterial antigens
- A61K39/085—Staphylococcus
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- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/12—Viral antigens
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
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- C07K14/195—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
- C07K14/305—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Micrococcaceae (F)
- C07K14/31—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Micrococcaceae (F) from Staphylococcus (G)
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Abstract
1. Иммуногенная композиция, включающая комбинацию антигенов, включающую два или более антигенов, выбранных из группы, состоящей из: (1) антигена sta006; (2) антигена sta011; (3) антигена esxA; (4) антигена esxB; (5) антигена hla; (6) антигена ebpS; (7) антигена efb; (8) антигена emp; (9) антигена esaC; (10) антигена coA; (11) антигена eap; (12) антигена FnBA; (13) антигена FnBB; (14) антигена ebhA; (15) антигена hlgB; (16) антигена hlgC; (17) антигена isdA; (18) антигена isdB; (19) антигена isdC; (20) антигена isdG; (21) антигена isdH; (22) антигена isdI; (23) антигена lukD; (24) антигена lukE; (25) антигена lukF; (26) антигена lukS; (27) антигена nuc; (28) антиген sasA; (29) антигена sasB; (30) антигена sasC; (31) антигена sasD; (32) антигена sasF; (33) антигена sdrC; (34) антигена sdrD; (35) антигена sdrE2; (36) антигена spa; (37) антигена clfA; (38) антигена clfB; (39) антигена sta001; (40) антигена sta002; (41) антигена sta003; (42) антигена sta004; (43) антигена sta005; (44) антигена sta007; (45) антигена sta008; (46) антигена sta009; (47) антигена sta010; (48) антигена sta012; (49) антигена sta013; (50) антигена sta014; (51) антигена sta015; (52) антигена sta016; (53) антигена sta017; (54) антигена sta018; (55) антигена sta019; (56) антигена sta020; (57) антигена sta021; (58) антигена sta022; (59) антигена sta023; (60) антигена sta024; (61) антигена sta025; (62) антигена sta026; (63) антигена sta027; (64) антигена sta028; (65) антигена sta029;(66) антигена sta030; (67) антигена sta031; (68) антигена sta032; (69) антигена sta033; (70) антигена sta034; (71) антигена sta035; (72) антигена sta036; (73) антигена sta037; (74) антигена sta038; (75) антигена sta039; (76) антигена sta040; (77) антигена sta041; (78) антигена sta042; (79) антигена sta043; (80) антигена sta044; (81) антигена sta045; (82) антигена sta046; (83) антигена sta047; (84) антигена sta048; (85) антигена sta049; (86) антигена sta050; (87) антигена sta051; (88) антигена sta052; (89) антигена sta053; (90) антигена sta054; (91) антигена sta055; (92) антигена sta056; (93) антигена sta057; (94) антигена sta058; (95) антигена sta059;
Claims (23)
1. Иммуногенная композиция, включающая комбинацию антигенов, включающую два или более антигенов, выбранных из группы, состоящей из: (1) антигена sta006; (2) антигена sta011; (3) антигена esxA; (4) антигена esxB; (5) антигена hla; (6) антигена ebpS; (7) антигена efb; (8) антигена emp; (9) антигена esaC; (10) антигена coA; (11) антигена eap; (12) антигена FnBA; (13) антигена FnBB; (14) антигена ebhA; (15) антигена hlgB; (16) антигена hlgC; (17) антигена isdA; (18) антигена isdB; (19) антигена isdC; (20) антигена isdG; (21) антигена isdH; (22) антигена isdI; (23) антигена lukD; (24) антигена lukE; (25) антигена lukF; (26) антигена lukS; (27) антигена nuc; (28) антиген sasA; (29) антигена sasB; (30) антигена sasC; (31) антигена sasD; (32) антигена sasF; (33) антигена sdrC; (34) антигена sdrD; (35) антигена sdrE2; (36) антигена spa; (37) антигена clfA; (38) антигена clfB; (39) антигена sta001; (40) антигена sta002; (41) антигена sta003; (42) антигена sta004; (43) антигена sta005; (44) антигена sta007; (45) антигена sta008; (46) антигена sta009; (47) антигена sta010; (48) антигена sta012; (49) антигена sta013; (50) антигена sta014; (51) антигена sta015; (52) антигена sta016; (53) антигена sta017; (54) антигена sta018; (55) антигена sta019; (56) антигена sta020; (57) антигена sta021; (58) антигена sta022; (59) антигена sta023; (60) антигена sta024; (61) антигена sta025; (62) антигена sta026; (63) антигена sta027; (64) антигена sta028; (65) антигена sta029; (66) антигена sta030; (67) антигена sta031; (68) антигена sta032; (69) антигена sta033; (70) антигена sta034; (71) антигена sta035; (72) антигена sta036; (73) антигена sta037; (74) антигена sta038; (75) антигена sta039; (76) антигена sta040; (77) антигена sta041; (78) антигена sta042; (79) антигена sta043; (80) антигена sta044; (81) антигена sta045; (82) антигена sta046; (83) антигена sta047; (84) антигена sta048; (85) антигена sta049; (86) антигена sta050; (87) антигена sta051; (88) антигена sta052; (89) антигена sta053; (90) антигена sta054; (91) антигена sta055; (92) антигена sta056; (93) антигена sta057; (94) антигена sta058; (95) антигена sta059; (96) антигена sta060; (97) антигена sta061; (98) антигена sta062; (99) антигена sta063; (100) антигена sta064; (101) антигена sta065; (102) антигена sta066; (103) антигена sta067; (104) антигена sta068; (105) антигена sta069; (106) антигена sta070; (107) антигена sta071; (108) антигена sta072; (109) антигена sta073; (110) антигена sta074; (111) антигена sta075; (112) антигена sta076; (113) антигена sta077; (114) антигена sta078; (115) антигена sta079; (116) антигена sta080; (117) антигена sta082; (118) антигена sta083; (119) антигена sta084; (120) антигена sta085; (121) антигена sta086; (122) антигена sta087; (123) антигена sta088; (124) антигена sta089; (125) антигена sta090; (126) антигена sta091; (127) антигена sta092; (128) антигена sta093; (129) антигена sta094; (130) антигена sta095; (131) антигена sta096; (132) антигена sta097; (133) антигена sta098; (134) антигена sta099; (135) антигена sta100; (136) антигена sta101; (137) антигена sta102; (138) антигена sta103; (139) антигена sta104; (140) антигена sta105; (141) антигена sta106; (142) антигена sta107; (143) антигена sta108; (144) антигена sta109; (145) антигена sta110; (146) антигена sta111; (147) антигена sta112; (148) антигена sta113; (149) антигена sta114; (150) антигена sta115; (151) антигена sta116; (152) антигена sta117; (153) антигена sta118; (154) антигена sta119; (155) антигена sta120; (156) антигена NW_6; (157) антигена NW_9; (158) антигена NW_10; (159) антигена NW_7; (160) антигена NW_8; (161) антигена NW_2; (162) антигена NW_1; (163) антигена sta081; и (164) антигена NW_5.
2. Композиция по п.1, включающая, по меньшей мере, один антиген, выбранный из номеров (3)-(38), и, по меньшей мере, один антиген, выбранный из номеров (1), (2) и (37)-(149).
3. Композиция по п.2, включающая:
по меньшей мере, один антиген, выбранный из номеров (37), (38), (8), (9), (3), (4), (5), (17), (18), (19), (31), (32), (33), (34), (35) и (36); и
по меньшей мере, один антиген, выбранный из (40), (1), (43), (2), (64), (96), (133) и (147).
4. Композиция по п.1, включающая два или более антигенов, выбранных из группы, состоящей из: (1) антигена clfA; (2) антиген clfB; (3) антигена sdrE2; (4) антигена sdrC; (5) антигена SasF; (6) антигена emp; (7) антигена sdrD; (8) антигена spa; (9) антигена esaC; (10) антигена esxA; (11) антигена esxB; (12) антигена sta006; (13) антигена isdC; (14) антигена hla; (15) антигена sta011; (16) антигена isdA; (17) антигена isdB; (18) антигена sasF.
5. Композиция по п.1, включающая два или более антигенов, выбранных из группы, состоящей из: (1) антигена esxA; (2) антигена esxB; (3) антигена sta006; (4) антигена hla; (5) антигена sta011.
6. Композиция по п.1, включающая: (1) антиген esxA; (2) антиген esxB; (3) антиген sta006; (4) антиген hla; (S) антиген sta011.
7. Композиция по п.1, где один или более указанных антигенов адсорбированы на адъюванте гидроксиде алюминия, и, необязательно, где композиция включает гистидиновый буфер.
8. Композиция по п.1, дополнительно включающая: один или более конъюгатов (i) экзополисахарида S.aureus и (ii) белка-носителя.
9. Композиция по п.1, дополнительно включающая: один или более конъюгатов (i) капсулярного полисахарида S.aureus и (ii) белка-носителя.
10. Полипептид формулы NH2-A-{-X-L-}n-B-COOH, где:
X представляет собой аминокислотную последовательность стафилококкового антигена, выбранного из группы, состоящей из антигенов S.aureus: sta006, sta011, esxA, esxB, hla, clfA, clfB, coA, eap, ebhA, ebpS, efb, emp, esaC, FnBA, FnBB, hlgB, hlgC, isdA, isdB, isdC, isdG, isdH, isdI, lukD, lukE, lukF, lukS, nuc, sasA, sasB, sasC, sasD, sasF, sdrC, sdrD, sdrE2, spa, sta001, ataD02, sta003, sta004, sta005, sta007, sta00S, sta009, sta010, sta012, sta013, sta014, sta015, sta016, sta017, sta018, sta019, sta020, sta021, sta022, sta023, sta024, sta025, sta026, sta027, sta028, sta029, sta030, sta031, sta032, sta033, sta034, sta035, sta036, sta037, sta038, sta039, sta040, sta041, sta042, ata043, sta044, sta045, sta046, sta047, sta048, sta049, sta050, sta051, sta052, sta053, sta054, sta055, sta056, sta057, sta0S8, sta059, sta060, sta061, sta062, sta063, sta064, sta065, sta066, sta067, sta068, sta069, sta070, sta071, sta072, sta073, sta074, sta075, sta076, sta077, sta078, sta079, sta080, sta081, sta082, sta083, sta084, sta08S, sta086, sta087, sto088, sta089, sta090, sta091, sta092, sta093, sta094, sta095, sta096, sta097, sta098, sta099, sta100, sta101, sta102, sta103, sta104, sta105, sta106, sta107, sta108, sta109, sta110, sta111, sta112, sta113, sta114, sta115, sta116, sta117, sta118, NW_6, NW_9, NW_10, NW_7, NW_8, NW_2, NW_1 и NW_5;
L представляет собой необязательную линкерную аминокислотную последовательность;
A представляет собой необязательную N-концевую аминокислотную последовательность;
B представляет собой необязательную C-концевую аминокислотную последовательность; и
n представляет собой целое число, равное 2 или больше.
11. Полипептид по п.10, где антиген clfA может индуцировать антитело, которое узнает SEQ ID NO: 1 и включает аминокислотную последовательность: (a) обладающую 80% или большей идентичностью с SEQ ID NO: 1; и/или (b) включающую фрагмент, по меньшей мере, из 7 последовательных аминокислот SEQ ID NO: 1, где фрагмент включает эпитоп из SEQ ID NO: 1.
12. Иммуногенная композиция, включающая полипептид по п.10 и дополнительно включающая:
(A) один или более конъюгатов (i) экзополисахарида S. aureus и (il) белка-носителя; и/или
(B) один или более конъюгатов (i) капсулярного полисахарида S.aureus и (ii) белка-носителя.
13. Композиция по любому из пп.1-9 и 12, где антиген clfA может индуцировать антитело, которое узнает SEQ ID NO: 1 и включает аминокислотную последовательность: (a) обладающую 80% или большей идентичностью с SEQ ID NO: 1; и/или (b) включающую фрагмент, по меньшей мере, из 7 последовательных аминокислот SEQ ID NO: 1, где фрагмент включает эпитоп из SEQ ID NO: 1.
14. Полипептид, включающий аминокислотную последовательность: (a) обладающую 80% или большей идентичностью с SEQ ID NO: 151; и/или (b) включающую фрагмент, по меньшей мере, из 7 последовательных аминокислот из аминокислот 1-97 SEQ ID NO: 151 и, по меньшей мере, 7 последовательных аминокислот из аминокислот 104-207 SEQ ID NO: 151, где полипептид может индуцировать антитела, которые узнают как стафилококковый белок дикого типа, включающий SEQ ID NO: 10, так и стафилококковый белок дикого типа, включающий SEQ ID NO: 11.
15. Иммуногенная композиция, включающая полипептид по п.14 и один или более из следующих: (i) антиген sta006; (ii) антиген hla и/или (iii) антиген sta011.
16. Иммуногенная композиция, включающая полипептид по п.14 и (i) антиген sta006; (ii) антиген hla и (iii) антиген sta011.
17. Композиция по п.15 или 16, включающая адъювант.
18. Полипептид, включающий аминокислотную последовательность, обладающую 80% или большей идентичностью с аминокислотной последовательностью, выбранной из SEQ ID NO: 151, 152, 168, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 220, 221, 222, 223, 224, 237, 238, 241.
19. Полипептид, включающий аминокислотную последовательность, выбранную из SEQ ID NO: 151, 152, 168, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 220, 221, 222, 223, 224, 237, 238, 241, 242, 243, 244, 245.
20. Полипептид, включающий: (a) первую последовательность, обладающую 90% или большей идентичностью с SEQ ID NO: 218; и (b) вторую последовательность, обладающую 90% или большей идентичностью с SEQ ID NO: 219, где первая и вторая последовательности либо соединены непосредственно, либо соединены промежуточной аминокислотной последовательностью, содержащей менее 10 аминокислот.
21. Фармацевтическая композиция, включающая полипептид по любому из пп.14, 18, 19 и 20.
22. Способ индукции иммунного ответа у млекопитающего, включающий стадию введения млекопитающему эффективного количества полипептида или композиции по любому из предыдущих пунктов.
23. Нуклеиновая кислота, кодирующая полипептид по любому из пп.10, 14, 18, 19 и 20.
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