Magnitude and breadth of the neutralizing antibody response in the RV144 and Vax003 HIV-1 vaccine efficacy trials.

Magnitude and breadth of the neutralizing antibody response in the RV144 and Vax003 HIV-1 vaccine efficacy trials.
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DOI:
10.1093/infdis/jis367
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发表时间:
2012-08-01
期刊:
The Journal of infectious diseases
影响因子:
--
通讯作者:
Kim JH
Kim JH
中科院分区:
其他
文献类型:
--
作者:
Montefiori DC;Karnasuta C;Huang Y;Ahmed H;Gilbert P;de Souza MS;McLinden R;Tovanabutra S;Laurence-Chenine A;Sanders-Buell E;Moody MA;Bonsignori M;Ochsenbauer C;Kappes J;Tang H;Greene K;Gao H;LaBranche CC;Andrews C;Polonis VR;Rerks-Ngarm S;Pitisuttithum P;Nitayaphan S;Kaewkungwal J;Self SG;Berman PW;Francis D;Sinangil F;Lee C;Tartaglia J;Robb ML;Haynes BF;Michael NL;Kim JH

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背景:一种表达人类免疫缺陷病毒1型(HIV-1)Gag、Pro和膜连接gp 120(vCP 1521)的重组金丝雀痘病毒载体,与二价gp 120蛋白加强免疫(AIDSVAX B/E)相结合,在泰国社区人群中提供了适度的HIV-1感染保护(RV 144试验)。 在仅接受AIDSVAX B/E的泰国注射吸毒者中未观察到保护作用(Vax 003试验)。我们比较了这两项试验中的中和抗体应答。方法:在TZM-b1和A3 R5细胞中用1级和2级病毒株评估中和作用。 结果:在RV 144和Vax 003中检测到几种1级病毒的中和作用。 Vax 003中的峰值滴度较高,并且在两项试验中迅速减弱。RV 144中的应答部分靶向gp 120的V3。vCP 1521初免加2次gp 120蛋白加强接种优于2次gp 120蛋白单独接种,证实了vCP 1521的初免效应。仅在Vax 003和A3 R5细胞中检测到2级病毒的零星弱中和。结论:研究结果表明,在低风险异性恋人群中,弱中和抗体应答可以部分保护HIV-1,或者RV 144中观察到的适度疗效是由其他免疫应答介导的,无论是单独的还是与中和抗体联合使用。 
Background. 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. Methods. Neutralization was assessed with tier 1 and tier 2 strains of virus in TZM-bl and A3R5 cells. Results. 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. Conclusion. 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.
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