Liao Hua-Xin, Sutherland Laura L, Xia Shi-Mao, Brock Mary E, Scearce Richard M, Vanleeuwen Stacie, Alam S Munir, McAdams Mildred, Weaver Eric A, Camacho Zenaido, Ma Ben-Jiang, Li Yingying, Decker Julie M, Nabel Gary J, Montefiori David C, Hahn Beatrice H, Korber Bette T, Gao Feng, Haynes Barton F
Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
Virology. 2006 Sep 30;353(2):268-82. doi: 10.1016/j.virol.2006.04.043.
HIV-1 subtype C is the most common HIV-1 group M subtype in Africa and many parts of Asia. However, to date HIV-1 vaccine candidate immunogens have not induced potent and broadly neutralizing antibodies against subtype C primary isolates. We have used a centralized gene strategy to address HIV-1 diversity and generated a group M consensus envelope gene with shortened consensus variable loops (CON-S) for comparative studies with wild-type (WT) Env immunogens. Our results indicate that the consensus HIV-1 group M CON-S Env elicited cross-subtype neutralizing antibodies of similar or greater breadth and titer than the WT Envs tested, indicating the utility of a centralized gene strategy. Our study also shows the feasibility of iterative improvements in Env immunogenicity by rational design of centralized genes.
HIV-1 C亚型是非洲和亚洲许多地区最常见的HIV-1 M组亚型。然而,迄今为止,HIV-1候选疫苗免疫原尚未诱导出针对C亚型原始分离株的强效且广泛中和的抗体。我们采用了集中化基因策略来应对HIV-1的多样性,并生成了一个具有缩短的共有可变环(CON-S)的M组共有包膜基因,用于与野生型(WT)Env免疫原进行比较研究。我们的结果表明,共有HIV-1 M组CON-S Env诱导出的交叉亚型中和抗体的广度和效价与所测试的WT Env相似或更高,这表明集中化基因策略的实用性。我们的研究还表明,通过对集中化基因进行合理设计来迭代改善Env免疫原性是可行的。