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首页> 外文期刊>The Journal of Infectious Diseases >A trimeric, V2-deleted HIV-1 envelope glycoprotein vaccine elicits potent neutralizing antibodies but limited breadth of neutralization in human volunteers.
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A trimeric, V2-deleted HIV-1 envelope glycoprotein vaccine elicits potent neutralizing antibodies but limited breadth of neutralization in human volunteers.

机译：一种三聚体，缺失V2的HIV-1包膜糖蛋白疫苗可引发有效的中和抗体，但在人类志愿者中产生的中和范围有限。

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摘要

BACKGROUND: A key missing element in the development of a successful human immunodeficiency virus (HIV) vaccine is an immunogen that can generate broadly cross-neutralizing antibodies against primary isolates of the virus. METHODS: This phase 1 clinical trial employed a DNA prime and subunit envelope protein boost in an attempt to generate cellular and humoral immune responses that might be desirable in a protective HIV vaccine. Priming was performed via intramuscular injection with gag and env DNA adsorbed to polylactide coglycolide microspheres, followed by boosting with a recombinant trimeric envelope (Env) glycoprotein delivered in MF59 adjuvant. RESULTS: The DNA prime and protein boost were generally safe and well-tolerated. Env-specific CD4(+) cellular responses were generated that were predominantly detected after Env protein boosting. Neutralizing antibody responses against the homologous SF162 viral isolate were remarkably strong and were present in the majority of vaccine recipients, including a strong response against CD4-induced epitopes on gp120. Despite the promising potency of this vaccine approach, neutralization breadth against heterologous tier 2 strains of HIV-1 was minimal. CONCLUSIONS: Potent neutralization against neutralization-sensitive strains of HIV is achievable in humans through a DNA prime, recombinant oligomeric Env protein boost regimen. Eliciting substantial breadth of neutralization remains an elusive goal. CLINICAL TRIALS REGISTRATION: NCT00073216.
机译：背景：成功的人类免疫缺陷病毒（HIV）疫苗开发中的一个关键缺失要素是一种免疫原，可以产生针对该病毒主要分离株的广泛交叉中和抗体。方法：该1期临床试验采用DNA初免和亚基包膜蛋白增强技术，试图产生保护性HIV疫苗可能需要的细胞和体液免疫应答。通过肌肉注射gag和env DNA吸附到聚丙交酯乙交酯微球上进行引物引发，然后用在MF59佐剂中递送的重组三聚体包膜（Env）糖蛋白加强免疫。结果：DNA引物和蛋白质增强通常是安全的，并且耐受性良好。 Env特异的CD4（+）细胞反应产生，主要是在Env蛋白加强后检测到的。针对同源SF162病毒分离株的中和抗体应答非常强，并且存在于大多数疫苗接种者中，包括针对gp120上CD4诱导的表位的强烈应答。尽管这种疫苗方法前景广阔，但针对HIV-1异源2级菌株的中和广度却很小。结论：通过DNA初免，重组的低聚Env蛋白增强方案，可以在人类中实现对HIV中和敏感株的有效中和。消除广泛的中和仍然是一个遥不可及的目标。临床试验注册：NCT00073216。

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