疫苗诱导产生的针对HIV-1 gp120第三可变区的人抗体对感染病毒施加免疫压力。

Vaccine-induced Human Antibodies Specific for the Third Variable Region of HIV-1 gp120 Impose Immune Pressure on Infecting Viruses.

作者信息

Zolla-Pazner Susan, Edlefsen Paul T, Rolland Morgane, Kong Xiang-Peng, deCamp Allan, Gottardo Raphael, Williams Constance, Tovanabutra Sodsai, Sharpe-Cohen Sandra, Mullins James I, deSouza Mark S, Karasavvas Nicos, Nitayaphan Sorachai, Rerks-Ngarm Supachai, Pitisuttihum Punnee, Kaewkungwal Jaranit, O'Connell Robert J, Robb Merlin L, Michael Nelson L, Kim Jerome H, Gilbert Peter

机构信息

New York Veterans Affairs Harbor Healthcare System, 423 East 23 Street, New York, NY 10010, USA ; New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA.

Vaccine and Infectious Disease Division, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., M2-C200, Seattle, WA 98109, USA.

出版信息

EBioMedicine. 2014 Nov 1;1(1):37-45. doi: 10.1016/j.ebiom.2014.10.022.

To evaluate the role of V3-specific IgG antibodies (Abs) in the RV144 clinical HIV vaccine trial, which reduced HIV-1 infection by 31.2%, the anti-V3 Ab response was assessed. Vaccinees' V3 Abs were highly cross-reactive with cyclic V3 peptides (cV3s) from diverse virus subtypes. Sieve analysis of CRF01_AE breakthrough viruses from 43 vaccine- and 66 placebo-recipients demonstrated an estimated vaccine efficacy of 85% against viruses with amino acids mismatching the vaccine at V3 site 317 (p=0.004) and 52% against viruses matching the vaccine at V3 site 307 (p=0.004). This analysis was supported by data showing vaccinees' plasma Abs were less reactive with I replaced with residues found more often in vaccinees' breakthrough viruses. Simultaneously, viruses with mutations at F were less infectious, possibly due to the contribution of F to optimal formation of the V3 hydrophobic core. These data suggest that RV144-induced V3-specific Abs imposed immune pressure on infecting viruses and inform efforts to design an HIV vaccine.

为评估V3特异性IgG抗体（Abs）在RV144临床HIV疫苗试验中的作用（该试验使HIV-1感染率降低了31.2%），对其抗V3抗体反应进行了评估。疫苗接种者的V3抗体与来自不同病毒亚型的环状V3肽（cV3s）具有高度交叉反应性。对43名疫苗接种者和66名安慰剂接受者的CRF01_AE突破性病毒进行筛选分析表明，对于V3位点317处氨基酸与疫苗不匹配的病毒，估计疫苗效力为85%（p = 0.004），对于V3位点307处与疫苗匹配的病毒，疫苗效力为52%（p = 0.004）。这一分析得到了相关数据的支持，这些数据显示，疫苗接种者血浆抗体与用疫苗接种者突破性病毒中更常见的残基替代I后的反应性较低。同时，F位点发生突变的病毒传染性较低，这可能是由于F对V3疏水核心的最佳形成有贡献。这些数据表明，RV144诱导的V3特异性抗体对感染病毒施加了免疫压力，并为设计HIV疫苗的努力提供了信息。