Does the key to a successful HIV type 1 vaccine lie among the envelope sequences of infected individuals?
Does the key to a successful HIV type 1 vaccine lie among the envelope sequences of infected individuals?
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1 型 HIV 疫苗成功的关键是否在于感染个体的包膜序列？
DOI：
10.1089/aid.1995.11.1131
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Hurwitz,JL
中科院分区：
文献类型：
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作者：
Rencher,SD;Slobod,KS;Dawson,DH;Lockey,TD;Hurwitz,JL
为了开发疫苗，我们从两个无症状的HIV-1感染者的血液样本(A和B)中分离了env序列。样本A来自2个月前HIV-1血清检测呈阴性的个人。样本B来自一名血清转换日期未知的个人。如表1所示，供体A血清样本中和了实验室库存病毒HTLVIIIB(见参考文献)。2详细方法)，但未能中和一次分离株，500。另外，样品B显示了对三种被测病毒的中和抗体活性，包括(1)在CEMSS细胞上测试的HTLV-IIIB，(2)在CEMSS细胞上测试的500，以及(3)在外周血单核细胞(PBMC)上测试的第二个初级分离株1028。我们通过聚合酶链式反应(PCR)从A、B血源DNA中扩增出ERV编码序列，并将其克隆到基于pSC11的env表达载体pVenv4中。3和4为详细信息)。从每个样本中获得了大量克隆。重组克隆的VI、V2和V3区的预测氨基酸序列如图1和图2所示。正如所证明的那样，来自供体A样本的包膜蛋白的多样性比来自供体B的更加有限。对于供体B，最大的多样性发生在V2环中，那里存在大量的缺失、替换和插入。对V4和V5区域的初步分析显示，与V2区域相比，差异相对较小(数据未显示)。来自供体B的env V3序列缺乏许多美国分离株所特有的GPGRAF序列。大多数核苷酸差异导致氨基酸差异。这些研究表明，供体B的env序列的多样性和抗体中和能力的广度均优于供体A。不同的env呈递给免疫系统可能有助于产生保护性免疫。在接触艾滋病毒之后，个人基本上会受到多轮感染。也就是说，随着中和免疫反应的产生迫使病毒逃逸突变体的选择，进而引发一系列新的
For the purpose of vaccine development, we have isolated env sequences from blood samples (A and B) from two asymptomatic HIV-1-infected individuals. Sample A was from an in-dividual who had testedHIV-1 seronegative 2 months previously. Sample B was from an individual whose date of seroconversion was unknown. As shown in Table 1, the donor A serum sample neutralized the laboratory stock virus HTLVIIIB (see Ref. 2 for detailed methods), but failed to neutralize a primary isolate, 500. Alternatively, sample B demonstrated neutralizing antibody activity against three tested viruses in-cluding (1) HTLV-IIIB, tested on CEMSS cells,(2) 500, tested on CEMSS cells, and (3) 1028, a second primary isolate tested on peripheral blood mononuclear cells (PBMCs). We amplified ercv-encoding sequences from A and B bloodderived DNA by the polymerase chain reaction (PCR), and cloned the fragments by substitution into pVenv4, a pSCll-based env expression vector (see Refs. 3 and 4 for details). Numerous clones were obtained from each sample. Predicted amino acid sequences for the VI, V2, and V3 regions of re-sultant clones are aligned in Figs. 1 and 2. As demonstrated, the diversity of env from the donor A sample was more limited than that from donor B. For donor B, the greatest diversity was in the V2 loop, where deletions, substitutions, and insertions were prevalent. Preliminary analyses of V4 and V5 regions showed relatively little diversity in comparison to that of the V2 region (data not shown). The env V3 sequences from donor B lacked theGPGRAF sequence known to characterize many US isolates. Most nucleotide differences resulted in amino acid differences. It appeared from these studies that the diversity of env sequences and the breadth of antibody neutralization ca-pacity were each superior in donor B as compared to donor A. It is likely that presentation of diverse Env to the immune system contributes to the generation of protective immunity. Following HIV exposure, individuals are essentially subjected to multiple rounds of infection. That is, a cycle progresses as the generation of a neutralizing immune response forces the se-lection of viral escape mutants that in turn elicit a new set of