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Recombinant MVA viruses expressing HIV env, gag and pol modified HIV clade A / G, clade B, and clade C genes

机译:表达HIV env,gag和pol修饰的HIV进化枝A / G,进化枝B和进化枝C基因的重组MVA病毒

摘要

A pharmaceutical composition comprising a recombinant MVA virus expressing an HIV env, gag-pol or modified gene thereof for the production of an HIV Env, Gag-Pol antigen by expression from said recombinant MVA virus, where it is modified said HIV env gene to encode an HIV Env protein composed of gp120 and the transmembrane and ectodomain domain of gp41 but lacking part or all of the cytoplasmic domain of gp41, and a pharmaceutically acceptable carrier; wherein said env gene, HIV gag-pol or modified gene thereof is taken from the clade AG and said HIV env gene or modified gene thereof is at least 97% identical to the sequence set forth in Figure 12, and said HIV gag-pol gene or modified gene thereof is at least 97% identical to the sequence set forth in Figure 13, and wherein the pol gene encodes an asparagine in amino acid 185 of the reverse transcriptase, a threonine in the amino acid 266 of reverse transcriptase and a glutamine in amino acid 478 of reverse transcriptase; or said env, gag-pol HIV or modified gene thereof is taken from clade B and said HIV env gene or modified gene thereof is at least 97% identical to the sequence set forth in Figure 23, and said gene HIV gag-pol or modified gene thereof is at least 97% identical to the sequence set forth in Figure 24, and wherein the pol gene encodes an asparagine in amino acid 185 of the reverse transcriptase, a threonine in amino acid 266 of reverse transcriptase and a glutamine in amino acid 478 of reverse transcriptase; or said env, gag-pol or modified gene thereof is taken from clade C and said HIV env or modified gene thereof is at least 97% identical to the sequence set forth in Figure 39, and said gene HIV gag-pol or modified gene thereof is at least 97% identical to the sequence set forth in Figure 40, and wherein the pol gene encodes an asparagine in amino acid 185 of the reverse transcriptase, a threonine in amino acid 266 of reverse transcriptase and a glutamine in amino acid 478 of reverse transcriptase; wherein said env gene is inserted into deletion II of the MVA virus and said gag-pol gene is inserted into deletion III of the MVA virus; and wherein said env gene and said gag-pol gene are under the control of the mH5 promoter.
机译:包含表达HIV env,gag-pol或其修饰基因的重组MVA病毒的药物组合物,用于通过从所述重组MVA病毒表达而产生HIV Env,Gag-Pol抗原,其中将所述HIV env基因修饰为编码一种HIV Env蛋白,由gp120和gp41的跨膜和胞外域结构域组成,但缺少gp41的部分或全部胞质结构域,以及药学上可接受的载体;其中所述env基因,HIV gag-pol或其修饰基因取自进化枝AG,并且所述HIV env基因或其修饰基因与图12所示的序列至少97%相同,并且所述HIV gag-pol基因或其修饰的基因与图13所示的序列至少97%相同,其中pol基因编码逆转录酶的氨基酸185中的天冬酰胺,逆转录酶的氨基酸266中的苏氨酸和谷氨酰胺。逆转录酶的氨基酸478;或所述env,gag-pol HIV或其修饰基因取自进化枝B,且所述HIV env基因或其修饰基因与图23所示序列至少97%相同,所述HIV gag-pol基因或修饰基因其基因与图24所示的序列具有至少97%的同一性,并且其中pol基因编码逆转录酶的氨基酸185中的天冬酰胺,逆转录酶的氨基酸266中的苏氨酸和氨基酸478中的谷氨酰胺。逆转录酶;或者其env,gag-pol或其修饰基因取自进化枝C,并且所述HIV env或其修饰基因与图39所示的序列至少97%相同,并且所述基因HIV gag-pol或其修饰基因与图40所示的序列具有至少97%的同一性,并且其中pol基因编码逆转录酶的氨基酸185中的天冬酰胺,逆转录酶的氨基酸266中的苏氨酸和逆转录氨基酸478中的谷氨酰胺。转录酶其中所述env基因插入MVA病毒的缺失II,所述gag-pol基因插入MVA病毒的缺失III。其中所述env基因和所述gag-pol基因在mH5启动子的控制下。

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