RU2015122368A - Слитые белки для применения в качестве иммуногенных усиливающих агентов для индуцирования антигенспецифического т-клеточного ответа - Google Patents

Слитые белки для применения в качестве иммуногенных усиливающих агентов для индуцирования антигенспецифического т-клеточного ответа Download PDF

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RU2015122368A
RU2015122368A RU2015122368A RU2015122368A RU2015122368A RU 2015122368 A RU2015122368 A RU 2015122368A RU 2015122368 A RU2015122368 A RU 2015122368A RU 2015122368 A RU2015122368 A RU 2015122368A RU 2015122368 A RU2015122368 A RU 2015122368A
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amino acid
fusion protein
binding domain
seq
protein according
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RU2015122368A
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RU2619187C2 (ru
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Вэй-И ЧОУ
Чиа-Мао У.
Цзюнь-Мин У.
Сиу-Кан ЧАН
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Тевакс Дженетикс Вэксин Ко., Лтд.
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Claims (30)

1. Слитый белок, содержащий:
(a) домен связывания с антигенпрезентирующей клеткой (АПК) или домен связывания с рецептором CD91, расположенный на N-конце слитого белка;
(b) транслокационный пептид длиной от 34 до 112 аминокислотных остатков, содержащий аминокислотную последовательность, которая по меньшей мере на 90% идентична SEQ ID NO: 4, 2, 3 или 6, расположенный на С-конце домена связывания с АПК или домена связывания с рецептором CD91;
(c) антиген патогена, расположенный на С-конце транслокационного пептида;
(d) сигнал ядерного экспорта, содержащий аминокислотную последовательность SEQ ID NO: 13; и
(e) последовательность, обеспечивающую удержание в эндоплазматическом ретикулуме, расположенную на С-конце слитого белка.
2. Слитый белок по п. 1, отличающийся тем, что домен связывания с АПК или домен связывания с CD91 рецептором, является полипептидом, содержащим аминокислотную последовательность, которая по меньшей мере на 90% идентична последовательности, выбранной из группы, состоящей из SEQ ID NO: 1 и с 8 по 11.
3. Слитый белок по п. 1, отличающийся тем, что сигнал ядерного экспорта содержит аминокислотную последовательность SEQ ID NO: 14.
4. Слитый белок по п. 1, отличающийся тем, что последовательность, обеспечивающая удержание в эндоплазматическом ретикулуме, содержит аминокислотную последовательность SEQ ID NO: 15.
5. Слитый белок по п. 1, отличающийся тем, что сигнал ядерного экспорта расположен между транслокационным пептидом и антигеном.
6. Слитый белок по п. 1, отличающийся тем, что сигнал ядерного экспорта расположен между антигеном и последовательностью, обеспечивающей удержание в эндоплазматическом ретикулуме.
7. Слитый белок по п. 1, отличающийся тем, что сигнал ядерного экспорта и последовательность, обеспечивающая удержание в эндоплазматическом ретикулуме, образуют слитый пептид, содержащий аминокислотную последовательность, которая по меньшей мере на 90% идентична SEQ ID NO: 12.
8. Слитый белок по п. 1, отличающийся тем, что транслокационный пептид имеет длину, лежащую в диапазоне от 34 аминокислотных остатков до 61 аминокислотного остатка.
9. Слитый белок по п. 1, отличающийся тем, что домен связывания с АПК или домен связывания с CD91 рецептором не содержит аминокислотной последовательности домена I связывания экзотоксина A Pseudomonas (РЕ).
10. Слитый белок по п. 9, отличающийся тем, что домен связывания с АПК или домен связывания с CD91 рецептором содержит аминокислотную последовательность SEQ ID NO: 8.
11. Слитый белок по п. 1, отличающийся тем, что аминокислотная последовательность домена связывания с АПК или домена связывания с CD91 рецептором является последовательностью SEQ ID NO: 1.
12. Слитый белок по п. 11, отличающийся тем, что транслокационный пептид имеет длину, лежащую в диапазоне от 34 аминокислотных остатков до 61 аминокислотного остатка.
13. Слитый белок по п. 12, отличающийся тем, что сигнал ядерного экспорта и последовательность, обеспечивающая удержания в эндоплазматическом ретикулуме, образуют слитый пептид с аминокислотной последовательностью, которая по меньшей мере на 90% идентична SEQ ID NO: 12.
14. Слитый белок по п. 11, отличающийся тем, что транслокационный пептид имеет длину, лежащую в диапазоне от 34 аминокислотных остатков до 46 аминокислотных остатков.
15. Слитый белок по п. 10, отличающийся тем, что транслокационный пептид имеет длину, лежащую в диапазоне от 34 аминокислотных остатков до 61 аминокислотного остатка.
16. Слитый белок по п. 15, отличающийся тем, что сигнал ядерного экспорта и последовательность, обеспечивающая удержания в эндоплазматическом ретикулуме, образуют слитый пептид с аминокислотной последовательностью, которая по меньшей мере на 90% идентична SEQ ID NO: 12.
17. Слитый белок по п. 1, отличающийся тем, что антиген является слитым антигеном, состоящим из двух или более антигенных пептидов из патогена.
18. Слитый белок по п. 1, отличающийся тем, что он по существу состоит из:
(a) домена связывания с антигенпрезентирующей клеткой (АПК) или домена связывания с рецептором CD91, расположенного на N-конце слитого белка;
(b) транслокационного пептида длиной от 34 до 112 аминокислотных остатков, содержащего аминокислотную последовательность, которая по меньшей мере на 90% идентична SEQ ID NO: 4, 2, 3 или 6, расположенного на С-конце домена связывания с АПК или домена связывания с рецептором CD91;
(c) антигена патогена, расположенного на С-конце транслокационного пептида;
(d) сигнала ядерного экспорта, содержащего аминокислотную последовательность SEQ ID NO: 13; и
(e) последовательности, обеспечивающей удержание в эндоплазматическом ретикулуме, расположенной на С-конце слитого белка.
19. Композиция вакцины, содержащая слитый белок по п. 1 и адъювант.
20. Способ индуцирования усиленных антигенспецифических Т-клеточных ответов против патогена, включающий введение композиции вакцины, содержащей терапевтически эффективное количество композиции вакцины по п. 19, субъекту, нуждающемуся в этом.
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