Development of Antibodies with Broad Neutralization Specificities against HIV-1 after Long Term SHIV Infection in Macaques
Development of Antibodies with Broad Neutralization Specificities against HIV-1 after Long Term SHIV Infection in Macaques
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DOI：
10.3390/v12020163
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发表时间：
2020-02-01
期刊：
影响因子：
4.7
通讯作者：
Gao, Feng
中科院分区：
文献类型：
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作者：
Gao, Nan;Gai, Yanxin;Gao, Feng
非人灵长类动物（NHP）是唯一适合评价HIV-1疫苗保护效力的动物模型。重要的是要了解如何以及何时在NHP中产生具有与人广泛中和抗体（bnAb）相似特异性的中和抗体（nAb）。为了解决这些问题，我们确定了血浆中和特异性在两个猕猴开发的中和宽度后，长期猿猴/人类免疫缺陷病毒（SHIV）感染，并确定了中和逃逸突变通过分析纵向血浆样品的env序列。使用25710 env突变体，靶向V2、CD 4 bs、V3和gp 120-gp 41界面的中和活性仅在来自猕猴G1015 R和G1020 R的第350周血浆中变得可检测。当用CAP 45 env突变体作图时，在G1015 R中在第217周仅检测到V2特异性，并持续至第350周。在CD 4 bs和V2区发现了中和逃逸突变。然而，所有这些都不同于针对人bnAb鉴定的那些耐药突变。这些结果表明，具有类似于人bnAb的特异性的nAb仅在长期SHIV感染后才可检测到，并且猕猴中的中和逃逸突变与HIV-1感染个体中发现的突变不同。这些发现可能对最佳利用NHP模型评估HIV-1疫苗具有重要意义。
Non-human primates (NHP) are the only animal model suitable to evaluate the protection efficacy of HIV-1 vaccines. It is important to understand how and when neutralizing antibodies (nAbs) with specificities similar to those of human broadly neutralizing antibodies (bnAbs) develop in NHPs. To address these questions, we determined plasma neutralization specificities in two macaques which developed neutralization breadth after long-term simian/human immunodeficiency virus (SHIV) infection and identified neutralization escape mutations by analyzing the env sequences from longitudinal plasma samples. Neutralization activities targeting V2, CD4bs, V3 and gp120-gp41 interface only became detectable in week 350 plasma from macaques G1015R and G1020R using 25710 env mutants. When mapped with CAP45 env mutants, only V2 specificity was detected at week 217 and persisted until week 350 in G1015R. Neutralization escape mutations were found in CD4bs and V2 regions. However, all of them were different from those resistant mutations identified for human bnAbs. These results show that nAbs with specificities similar to human bnAbs are only detectable after long-term SHIV infection and that neutralization escape mutations in macaques are different from those found in HIV-1-infected individuals. These findings can have important implications in the best utilization of the NHP model to evaluate HIV-1 vaccines.