Polyvalent vaccines for optimal coverage of potential T-cell epitopes in global HIV-1 variants
Polyvalent vaccines for optimal coverage of potential T-cell epitopes in global HIV-1 variants
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DOI：
10.1038/nm1461
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发表时间：
2007-01-01
期刊：
影响因子：
82.9
通讯作者：
Korber, Bette T.
中科院分区：
文献类型：
--
作者：
Fischer, Will;Perkins, Simon;Korber, Bette T.
HIV-1/艾滋病疫苗必须解决HIV-1的极端多样性。我们已经设计了新的多价疫苗抗原组成的“镶嵌”蛋白，通过计算优化方法从天然序列的片段组装。镶嵌蛋白类似于天然蛋白，并且镶嵌组最大化病毒群体的潜在T细胞表位（九个氨基酸的肽）的覆盖。我们发现，使用马赛克的病毒多样性的覆盖范围大大增加了覆盖范围相比，自然序列的候选疫苗，可变和保守的蛋白质;保守的HIV-1蛋白，全球覆盖可能是可行的。例如，四种嵌合蛋白完全匹配全球Gag序列中74%的9个氨基酸潜在表位; 87%的潜在表位匹配9个位置中的至少8个。相比之下，单一天然Gag蛋白仅覆盖37%（9/9）和67%（8/9）。嵌合体提供的多样性覆盖率可与数千个单独的肽所提供的多样性覆盖率相媲美，但是，由于天然蛋白质的片段被压缩成少量的天然样蛋白质，因此它们易于用于疫苗。
HIV-1/AIDS vaccines must address the extreme diversity of HIV-1. We have designed new polyvalent vaccine antigens comprised of sets of 'mosaic' proteins, assembled from fragments of natural sequences via a computational optimization method. Mosaic proteins resemble natural proteins, and a mosaic set maximizes the coverage of potential T-cell epitopes (peptides of nine amino acids) for a viral population. We found that coverage of viral diversity using mosaics was greatly increased compared to coverage by natural-sequence vaccine candidates, for both variable and conserved proteins; for conserved HIV-1 proteins, global coverage may be feasible. For example, four mosaic proteins perfectly matched 74% of 9-amino-acid potential epitopes in global Gag sequences; 87% of potential epitopes matched at least 8 of 9 positions. In contrast, a single natural Gag protein covered only 37% (9 of 9) and 67% (8 of 9). Mosaics provide diversity coverage comparable to that afforded by thousands of separate peptides, but, because the fragments of natural proteins are compressed into a small number of native-like proteins, they are tractable for vaccines.