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【主权项】
1. 一种融合蛋白，其包含至少一个核蛋白（NP)抗原的变体和鸡C4bp寡聚化域的变体。2. 根据权利要求1的融合蛋白，其中所述至少一个核蛋白抗原来自流感病毒株A、B或 Co3. 根据权利要求1或2的融合蛋白，其中所述核蛋白抗原是单体抗原。4. 根据权利要求3的融合蛋白，其中所述单体核蛋白抗原来自流感病毒株A，且呈现两 个下列点突变中的至少一个：E339A和R416A。5. 根据权利要求4的融合蛋白，其中所述单体核蛋白抗原由序列SEQ ID N0:2编码。6. 根据权利要求1至5的融合蛋白，其中所述鸡C4bp寡聚化域的变体是頂X313。7. 根据权利要求6的融合蛋白，其中頂X313呈现序列SEQ ID NO: 1。8. 根据权利要求1至5的融合蛋白，其中所述鸡C4bp寡聚化域的变体是頂X313载体 蛋白的变体，其包含具有序列ZXBBBBZ的至少一个带正电的肽的C-末端取代，其中（i) Z是 任何氨基酸或是缺失的，（ii)X是任何氨基酸和（iii)B是精氨酸（R)或赖氨酸（K)。9. 根据权利要求8的融合蛋白，其中所述頂X313载体蛋白的变体呈现序列SEQ ID NO:4 或 SEQ ID NO:5。10. 根据权利要求1至9中任一项的融合蛋白，其中所述NP抗原包含信号肽。11. 一种核酸，其编码根据权利要求1至10中任一项的融合蛋白。12. 根据权利要求11的编码融合蛋白的核酸，其中所述鸡C4bp寡聚化域的变体具有序 列 SEQ ID N0:4 或 SEQ ID N0:5。13. 根据权利要求12的核酸，其中其呈现序列SEQ ID NO:6或SEQ ID NO:7。14. 一种载体，其包含根据权利要求11至13的核酸。15. -种免疫原性组合物，其包含： _根据权利要求1至10中任一项的融合蛋白或根据权利要求11至13的核酸或根据权 利要求14的载体，和 -对于胞内TLRs的核酸配体。16. 根据权利要求15的免疫原性组合物，其中所述对于胞内TLRs的核酸配体是poly I:C〇17. 根据权利要求15或16中任一项的免疫原性组合物，其进一步包含疫苗佐剂。18. 根据权利要求15至17的免疫原性组合物，其用作用于预防和治疗流感疾病的疫苗 或免疫疗法。19. 一种用于增加对于流感的核蛋白抗原的细胞免疫响应的方法，其通过将具有SEQ ID N0:2中所示序列的核蛋白抗原融合于具有SEQ ID N0:4或SEQ ID N0:5中所示序列的 载体蛋白并且施用于人体或动物体中来进行。20. -种用于在有需要的人或动物中预防或治疗流感疾病的方法，其包括将权利要求 15至17中任一项的免疫原性组合物施用于所述人体或动物体中。
【专利摘要】本发明涉及一种融合蛋白，其包含来自流感病毒株A、B或C的核蛋白抗原的变体和C4bp寡聚化域的变体，用于增加来自流感的核蛋白抗原的细胞免疫原性。本发明还涉及核酸、载体、融合蛋白和免疫原性组合物，它们用作疫苗或免疫疗法用于预防和治疗流感疾病。
【IPC分类】C07K14/435, C07K14/445, C07K14/47
【公开号】CN105143251
【申请号】CN201480013364
【发明人】J·德尔坎波阿斯卡拉泰尔, F·希尔
【申请人】艾马克西欧
【公开日】2015年12月9日
【申请日】2014年3月18日
【公告号】CA2901888A1, US20150098958, WO2014147087A1