RU2005129727A - Конъюгаты пептида melan-a, аналога вирусно-подобной частицы - Google Patents
Конъюгаты пептида melan-a, аналога вирусно-подобной частицы Download PDFInfo
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- RU2005129727A RU2005129727A RU2005129727/13A RU2005129727A RU2005129727A RU 2005129727 A RU2005129727 A RU 2005129727A RU 2005129727/13 A RU2005129727/13 A RU 2005129727/13A RU 2005129727 A RU2005129727 A RU 2005129727A RU 2005129727 A RU2005129727 A RU 2005129727A
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Claims (25)
1. Композиция, содержащая
(a) вирусоподобную частицу;
(b) по меньшей мере одно иммуностимулирующее вещество; и
(c) по меньшей мере один антиген или антигенную детерминанту;
где указанный антиген или антигенная детерминанта связаны с указанной вирусоподобной частицей, и в которой указанное иммуностимулирующее вещество связано с указанной вирусоподобной частицей, и при этом указанный антиген содержит, альтернативно в основном состоит или альтернативно состоит из аналога пептида MelanA меланомы человека.
2. Композиция по п.1, где указанный по меньшей мере один антиген или антигенная детерминанта связаны с указанной вирусоподобной частицей по меньшей мере одной ковалентной связью, в котором, предпочтительно, указанная ковалентная связь является непептидной связью.
3. Композиция по п.1, где указанный аналог пептида MelanA меланомы человека характеризуется двумя предпочтительно одной аминокислотной заменой по сравнению с соответствующим нормальным пептидом MelanA, и где, кроме того, предпочтительно указанный аналог пептида MelanA меланомы человека имеет аминокислотную последовательность, выбранную из группы, включающей
(a) LAGIGILTV (SEQ ID NO:84);
(b) MAGIGILTV (SEQ ID NO:85);
(c) EAMGIGILTV (SEQ ID NO:86);
(d) ELAGIGILTV (SEQ ID NO:50);
(e) EMAGIGILTV (SEQ ID NO:87);
(f) YAAGIGILTV (SEQ ID NO:88); и
(g) FAAGIGILTV (SEQ ID NO:89).
4. Композиция по п.1, где указанный аналог пептида MelanA/MART-1 меланомы человека содержит, альтернативно в основном состоит или альтернативно состоит из последовательности ELAGIGILTV (SEQ ID NO: 50).
5. Композиция по п.1, где указанная вирусоподобная частица содержит по меньшей мере один первый сайт связывания, и в котором указанный антиген или антигенная детерминанта, кроме того, содержит по меньшей мере один второй сайт связывания, выбранный из группы, состоящей из
(a) сайта связывания, не встречающегося в природе c указанным антигеном или антигенной детерминантой; и
(b) сайта связывания, встречающегося в природе с указанным антигеном или антигенной детерминантой;
и где указанное связывание указанного антигена или антигенной детерминанты с указанной вирусоподобной частицей осуществляется посредством ассоциации между указанным первым сайтом связывания и указанным вторым сайтом связывания, при этом предпочтительно указанная ассоциация осуществляется посредством по меньшей мере одной непептидной связи, и при этом указанный антиген или антигенная детерминанта и указанная вирусоподобная частица взаимодействуют посредством указанной ассоциации с образованием упорядоченной и повторяющейся антигенной матрицы.
6. Композиция по п.5, где указанный первый сайт связывания содержит или предпочтительно состоит из аминогруппы или остатка лизина.
7. Композиция по п.5, где указанный второй сайт связывания содержит или, предпочтительно, состоит из сульфгидрильной группы или остатка цистеина.
8. Композиция по п.5, где указанным первым сайтом связывания является аминогруппа, а указанным вторым сайтом связывания является сульфгидрильная группа.
9. Композиция по п.5, где указанный аналог пептида MelanA/MART-1 меланомы человека с указанным вторым сайтом связывания имеет аминокислотную последовательность, выбранную из группы, включающей
(a) CGHGHSYTTAEELAGIGILTV (SEQ ID NO:55);
(b) CGGELAGIGILTV (SEQ ID NO:57);
(c) CSYTTAEELAGIGILTV ILGVL (SEQ ID NO:58);
(d) CGGELAGIGILTVILGVL (SEQ ID NO:59);
(e) ELAGIGILTVGGC (SEQ ID NO:60);
(f) CSPKSLELAGIGILTV (SEQ ID NO:92); и
(g) ELAGIGILTVILGVLGGC (SEQ ID NO:93).
10. Композиция по п.5, где указанный аналог пептида MelanA/MART-1 меланомы человека с указанным вторым сайтом связывания имеет аминокислотную последовательность CGHGHSYTTAEELAGIGILTV (SEQ ID NO:55).
11. Композиция по п.1, где указанной вирусоподобной частицей является рекомбинантная вирусоподобная частица, при этом предпочтительно указанная вирусоподобная частица выбрана из группы, включающей
(a) рекомбинантные белки вируса гепатита B;
(b) рекомбинантные белки вируса кори;
(c) рекомбинантные белки вируса Синдбис;
(d) рекомбинантные белки ротавируса;
(e) рекомбинантные белки вируса ящура;
(f) рекомбинантные белки ретровируса;
(g) рекомбинантные белки вируса Норуолк;
(h) рекомбинантные белки вируса папилломы;
(i) рекомбинантные белки вируса BK;
(j) рекомбинантные белки бактериофагов;
(k) рекомбинантные белки РНК-фагов;
(l) рекомбинантные белки Ty; и
(m) фрагменты любого из рекомбинантных белков (a)-(l).
12. Композиция по п.1, где указанная вирусоподобная частица содержит или альтернативно в основном состоит, или альтернативно состоит из рекомбинантных белков или их фрагментов РНК-фага, при этом предпочтительно указанный РНК-фаг выбран из группы, включающей
(a) бактериофаг Qв;
(b) бактериофаг R17;
(c) бактериофаг fr;
(d) бактериофаг GA;
(e) бактериофага SP;
(f) бактериофаг MS2;
(g) бактериофаг M11;
(h) бактериофаг MX1;
(i) бактериофаг NL95;
(j) бактериофаг f2;
(k) бактериофаг PP7; и
(l) бактериофаг AP205,
при этом, кроме того, предпочтительно указанная вирусоподобная частица содержит или альтернативно в основном состоит, или альтернативно состоит из рекомбинантных белков или их фрагментов бактериофага Qв или бактериофага AP205.
13. Композиция по п.1, где указанным иммуностимулирующим веществом является вещество, активирующее toll-подобный рецептор, или вещество, индуцирующее секрецию цитокина, при этом предпочтительно указанное вещество, активирующее toll-подобный рецептор, выбрано из группы, состоящей или альтернативно в основном состоящей из
(a) иммуностимулирующих нуклеиновых кислот;
(b) пептидогликанов;
(c) липополисахаридов;
(d) липотейхоновых кислот;
(e) соединений имидазохинолина;
(f) флагеллинов;
(g) липопротеидов;
(h) иммуностимулирующих органических молекул;
(i) неметилированных CpG-содержащих олигонуклеотидов; и
(j) любых смесей по меньшей мере одного вещества из (a), (b), (c), (d), (e), (f), (g), (h) и/или (i).
14. Композиция по п.13, где указанная иммуностимулирующая нуклеиновая кислота выбрана из группы, состоящей или альтернативно в основном состоящей из
(a) рибонуклеиновых кислот;
(b) дезоксирибонуклеиновых кислот;
(c) химерных нуклеиновых кислот; и
(d) любых смесей по меньшей мере одной нуклеиновой кислоты (a), (b) и/или (c) и
где предпочтительно указанная дезоксирибонуклеиновая кислота выбрана из группы, состоящей или альтернативно в основном состоящей из
(i) неметилированных CpG-содержащих олигонуклеотидов; и
(ii) олигонуклеотидов, не содержащих неметилированных мотивов CpG.
15. Композиция по п.1, где указанным иммуностимулирующим веществом является неметилированный CpG-содержащий олигонуклеотид.
16. Композиция по п.15, где указанный неметилированный CpG-содержащий олигонуклеотид содержит последовательность
5'X1X2CGX3X4 3',
и где X1, X2, X3 и X4 означают любой нуклеотид, и где предпочтительно по меньшей мере один из указанных нуклеотидов X1, X2, X3 и X4 имеет модификацию фосфатного остова.
17. Композиция по п.1, где указанное по меньшей мере одно иммуностимулирующее вещество и предпочтительно указанный неметилированный CpG-содержащий олигонуклеотид содержит или альтернативно в основном состоит, или альтернативно состоит из палиндромной последовательности.
18. Композиция по п.15, где указанный неметилированный CpG-содержащий олигонуклеотид содержит или альтернативно в основном состоит, или альтернативно состоит из последовательности GGGGGGGGGGGACGATCGTCGGGGGGGGGG (SEQ ID NO: 41).
19. Композиция по п.17, где указанная палиндромная последовательность содержит или альтернативно в основном состоит, или альтернативно состоит из GACGATCGTC (SEQ ID NO: 1).
20. Способ усиления иммунного ответа у животного, предусматривающий введение композиции по п.1 указанному животному, и где предпочтительно указанным животным является млекопитающее, и где, кроме того, предпочтительно указанным млекопитающим является человек.
21. Способ по п.20, где указанный иммунный ответ является усиленным B-клеточным ответом или усиленным T-клеточным ответом, при этом предпочтительно указанный T-клеточный ответ является ответом CTL или ответом Th-клеток, и при этом еще более предпочтительно указанный ответ Th-клеток является ответом Th1-клеток.
22. Способ по п.20, где указанную композицию вводят указанному животному подкожно, внутримышечно, внутривенно, интраназально и непосредственно в лимфатический узел.
23. Вакцина, содержащая иммунологически эффективное количество композиции по п.1 вместе с фармацевтически приемлемым разбавителем, носителем или эксципиентом, и при этом предпочтительно указанная вакцина, кроме того, содержит адъювант.
24. Способ иммунизации или лечения животного, предусматривающий введение указанному животному иммунологически эффективного количества вакцины по п.23 и где, предпочтительно, указанным животным является млекопитающее, и при этом, кроме того, предпочтительно указанным млекопитающим является человек.
25. Способ иммунизации или лечения животного, предусматривающий стадии примирования T-клеточного ответа у указанного животного и усиления T-клеточного ответа у указанного животного ревакцинацией, при этом указанное примирование или указанную ревакцинацию осуществляют введением иммунологически эффективного количества вакцины по п.23, и где предпочтительно указанное примирование и указанную ревакцинацию осуществляют введением иммунологически эффективного количества вакцины по п.23.
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