Schweighardt Becky, Liu Yang, Huang Wei, Chappey Colombe, Lie Yolanda S, Petropoulos Christos J, Wrin Terri
Monogram Biosciences, Inc., South San Francisco, CA, USA.
J Acquir Immune Defic Syndr. 2007 Sep 1;46(1):1-11. doi: 10.1097/QAI.0b013e318074eb5a.
We have developed an HIV-1 reference panel of 20 subtype B envelope clones isolated from the plasma of recently infected individuals. It is widely accepted that a prophylactic vaccine against HIV-1 requires the development of novel immunogens that are capable of eliciting broadly protective neutralizing antibody responses. Historically, patient serum has been screened for such antibodies by assaying against laboratory strains, but these viruses typically have increased neutralization sensitivity compared with primary isolates. To create a more standardized and relevant assay system for vaccine evaluation, we have developed a panel of primary envelopes derived from the plasma of individuals with documented acute/early subtype B HIV-1 infection occurring between 2000 and 2004. The HIV-1 envelopes from this panel vary in mode of transmission, coreceptor tropism, fusogenicity, and overall sensitivity to neutralization. These envelope sequences represent a broad spectrum of subtype B genetic diversity with an average pairwise genetic distance of 12% and a range from 10% to 19%. This well-characterized HIV-1 envelope panel should be a valuable resource for optimizing and standardizing vaccine assessment and improving vaccine design.
我们从近期感染个体的血浆中分离出20个B亚型包膜克隆,构建了一个HIV-1参考文库。人们普遍认为,一种预防HIV-1的疫苗需要开发能够引发广泛保护性中和抗体反应的新型免疫原。历史上,一直通过检测患者血清与实验室毒株的反应来筛查此类抗体,但与原始分离株相比,这些病毒通常具有更高的中和敏感性。为了创建一个更标准化且相关的疫苗评估检测系统,我们构建了一组主要包膜,其来源于2000年至2004年间记录在案的急性/早期B亚型HIV-1感染个体的血浆。该文库中的HIV-1包膜在传播方式、共受体嗜性、融合性以及对中和的总体敏感性方面存在差异。这些包膜序列代表了B亚型广泛的遗传多样性,平均成对遗传距离为12%,范围在10%至19%之间。这个特征明确的HIV-1包膜文库对于优化和标准化疫苗评估以及改进疫苗设计应是一种有价值的资源。