首页> 外国专利> POLYENV VACCINE AGANIST A HIV HUMAN, METHOD FOR MAKING HUMORAL AND/OR CELLULAR IMMUNE RESPONSE IN MAMMALS UPON HIV AND BI-FUNCTIONAL PLASMID

POLYENV VACCINE AGANIST A HIV HUMAN, METHOD FOR MAKING HUMORAL AND/OR CELLULAR IMMUNE RESPONSE IN MAMMALS UPON HIV AND BI-FUNCTIONAL PLASMID

机译:对抗HIV的POLYNERV疫苗,在HIV和双功能性疟疾中对哺乳动物进行免疫和/或细胞免疫反应的方法

摘要

1. A polyenv vaccine comprising at least 4 to about 10,000 different recombinant vaccinia viruses, each of them expresses a different variant of an env variant (EV) variant of a human immunodeficiency virus (HIV), wherein said EV nucleotide encodes both variable and constant regions of said envelope protein variant and said immunogenic composition is capable of eliciting at least one of a cellular and a humoral immmune response in a mammal against an HIV strain. 2. The polyenv according to claim 1, comprising from 10 to 100 recombinant viruses comprising different EV variants of HIV. 3. The polyenv according to claim 1, wherein the recombinant viruses are selected from the group consisting of vaccinia virus, canary pox virus, adenovirus and adeno-assosiated virus (AAV). 4. The polyenv according to claim 1, wherein different EV variant of HIV comprises gp120 and an oligomerization domain of gp41 sufficient to permit oligomerization of env proteins. 5. The polyenv according to claim 4, wherein different EV variants of HIV encode nucleotide, comprising comprises a KpnI-BsmI restriction fragment. 6. The polyenv according to claim 1, wherein the EV nucleotide sequence is isolated from patients infected with an HIV virus from a geographically restricted area or from patients infected with an HIV virus from different clades. 7. The polyenv according to claim 1, wherein the vaccine further comprises envelope protein variants expressed by the recombinant viruses. 8. The polyenv according to claim 1, wherein said immunogenic composition further comprises at least one of a pharmaceutically acceptable carrier, an adjuvant and an antiviral chemotherapeutic compound. 9. A method for making a humoral and/or cellular immune response in a mammal against a HIV human, comprising administering a mammal a vaccine in an effective amount, wherein the polyenv vaccine is used as a vaccine according to any of claims 1 to 8. 10. The method according to claim 9, wherein if a recombinant virus is a vaccinia virus then the polyenv virus is administered subcutaneously. 11. The method according to claim 9, wherein two polyenv vaccines are administered according to any of claims 1 to 8, in which the recombinant viruses are of a different species. 12. The method according to claim 9, wherein further comprising priming or boosting a humoral and/or cellular immune response by administering (a) an effective amount of at least one recombinant HIV env protein and/or (b) an effective amount of at least one DNA vector that codes on expression for a recombinant HIV env protein, wherein the DNA vector may be administered before, after or concurrently with the recombinant HIV env protein. 13. The method according to claim 9, wherein prior to administering the recombinant HIV env protein is mixed with an adjuvant. 14. The method according to claim 9, wherein the recombinant HIV evn protein is administered intramuscularly. 15. The method according to claim 9, wherein the recombinant HIV evn protein is mixed with an adjuvant and administered intramuscularly. 16. The method according to claim 9, wherein the DNA vector is administered with a gene gun. 17. A bi-functional plasmid used for producing recombinant viruses contained in the vaccine composition according to claim 1, comprising a xenogeneic gene, encoding a different envelope protein variant (EPV) of a immunoedeficiency virus (HIV) envelope protein, wherein the EPV contains both variable and constant regions, wherein said gene is under the control of expression sequences of two types, namely, the sequence is a cytomegalovirus immediate early (CMV) promoter and the sequence of a vaccinia virus early promoter and/or the sequence of a vaccinia virus late promoter.
机译:1.一种多环境疫苗,其包含至少4至约10,000种不同的重组牛痘病毒,它们各自表达人免疫缺陷病毒(HIV)的env变体(EV)变体的不同变体,其中所述EV核苷酸编码可变的和恒定的所述包膜蛋白变体的所述区域和所述免疫原性组合物能够引起哺乳动物针对HIV毒株的细胞和体液免疫反应中的至少一种。 2.根据权利要求1的多env,其包含10至100个重组病毒,其包含HIV的不同EV变体。 3.根据权利要求1所述的多环境,其中所述重组病毒选自牛痘病毒,金丝雀痘病毒,腺病毒和腺伴随病毒(AAV)。 4.根据权利要求1的多env,其中HIV的不同EV变体包含gp120和gp41的低聚结构域,该结构域足以允许env蛋白的低聚。 5.根据权利要求4所述的多环境,其中HIV的不同EV变体编码核苷酸,其包含KpnI-BsmI限制性片段。 6.根据权利要求1所述的多环境,其中所述EV核苷酸序列是从受地理限制区域感染HIV病毒的患者或从不同进化枝感染HIV病毒的患者中分离的。 7.根据权利要求1所述的多环境,其中所述疫苗还包含由重组病毒表达的包膜蛋白变体。 8.根据权利要求1所述的多环境,其中所述免疫原性组合物还包含药学上可接受的载体,佐剂和抗病毒化学治疗化合物中的至少一种。 9.一种在哺乳动物中针对HIV人进行体液和/或细胞免疫应答的方法,包括给哺乳动物施用有效量的疫苗,其中所述多包膜疫苗用作根据权利要求1至8中任一项的疫苗。 10.根据权利要求9的方法,其中如果重组病毒是痘苗病毒,则将多env病毒皮下给药。 11.根据权利要求9的方法,其中根据权利要求1至8中任一项施用两种多env疫苗,其中所述重组病毒是不同物种的。 12.根据权利要求9所述的方法,其中进一步包括通过施用(a)有效量的至少一种重组HIV env蛋白和/或(b)有效量的至少一种或多种抗体来引发或增强体液和/或细胞免疫应答。至少一种编码重组HIV env蛋白表达的DNA载体,其中该DNA载体可以在重组HIV env蛋白之前,之后或同时施用。 13.根据权利要求9的方法,其中在施用重组HIV env蛋白之前,将其与佐剂混合。 14.根据权利要求9的方法,其中所述重组HIV evn蛋白是肌内施用的。 15.根据权利要求9所述的方法,其中将所述重组HIV evn蛋白与佐剂混合并肌肉内施用。 16.根据权利要求9的方法,其中所述DNA载体与基因枪一起施用。 17.用于产生包含在权利要求1的疫苗组合物中的重组病毒的双功能质粒,其包含异种基因,其编码免疫缺陷病毒(HIV)包膜蛋白的不同包膜蛋白变体(EPV),其中所述EPV包含可变区和恒定区,其中所述基因在两种类型的表达序列的控制下,即,该序列是巨细胞病毒立即早期(CMV)启动子和牛痘病毒早期启动子的序列和/或牛痘序列病毒晚期启动子。

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