Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
J Infect Dis. 2012 Aug 1;206(3):431-41. doi: 10.1093/infdis/jis367. Epub 2012 May 25.
A recombinant canarypox vector expressing human immunodeficiency virus type 1 (HIV-1) Gag, Pro, and membrane-linked gp120 (vCP1521), combined with a bivalent gp120 protein boost (AIDSVAX B/E), provided modest protection against HIV-1 infection in a community-based population in Thailand (RV144 trial). No protection was observed in Thai injection drug users who received AIDSVAX B/E alone (Vax003 trial). We compared the neutralizing antibody response in these 2 trials.
Neutralization was assessed with tier 1 and tier 2 strains of virus in TZM-bl and A3R5 cells.
Neutralization of several tier 1 viruses was detected in both RV144 and Vax003. Peak titers were higher in Vax003 and waned rapidly in both trials. The response in RV144 was targeted in part to V3 of gp120.vCP1521 priming plus 2 boosts with gp120 protein was superior to 2 gp120 protein inoculations alone, confirming a priming effect for vCP1521. Sporadic weak neutralization of tier 2 viruses was detected only in Vax003 and A3R5 cells.
The results suggest either that weak neutralizing antibody responses can be partially protective against HIV-1 in low-risk heterosexual populations or that the modest efficacy seen in RV144 was mediated by other immune responses, either alone or in combination with neutralizing antibodies.
一种表达人类免疫缺陷病毒 1 型（HIV-1）Gag、Pro 和膜结合 gp120（vCP1521）的重组金丝雀痘载体，与二价 gp120 蛋白加强剂（AIDSVAX B/E）联合使用，在泰国的社区人群中提供了针对 HIV-1 感染的适度保护（RV144 试验）。在单独接受 AIDSVAX B/E 的泰国注射吸毒者中未观察到保护作用（Vax003 试验）。我们比较了这两项试验中的中和抗体反应。
使用 TZM-bl 和 A3R5 细胞中的 1 级和 2 级病毒株评估中和作用。
在 RV144 和 Vax003 中均检测到几种 1 级病毒的中和作用。Vax003 中的峰值滴度较高，且在两项试验中均迅速下降。RV144 中的反应部分针对 gp120 的 V3.vCP1521 引发加上 2 次 gp120 蛋白加强剂接种优于单独 2 次 gp120 蛋白接种，证实 vCP1521 具有引发作用。仅在 Vax003 和 A3R5 细胞中检测到对 2 级病毒的零星弱中和作用。
结果表明，在低风险异性恋人群中，弱中和抗体反应可能部分具有针对 HIV-1 的保护作用，或者在 RV144 中观察到的适度疗效是由其他免疫反应介导的，无论是单独还是与中和抗体联合介导的。
