Prevalence of broadly neutralizing antibody responses during chronic HIV-1 infection.
Prevalence of broadly neutralizing antibody responses during chronic HIV-1 infection.
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DOI：
10.1097/qad.0000000000000106
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发表时间：
2014-01-14
期刊：
影响因子：
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通讯作者：
Korber BT
中科院分区：
文献类型：
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作者：
Hraber P;Seaman MS;Bailer RT;Mascola JR;Montefiori DC;Korber BT
对HIV-1感染者中和抗体的研究提供了对疫苗和设计有效免疫原的方法可能引起的反应质量的见解。一些人产生了特别令人感兴趣的高滴度的特殊广泛反应性中和抗体;然而，更温和的反应可能是疫苗的合理目标。我们进行了一项大规模的横断面研究，以确定慢性HIV-1感染期间所见的中和效力和宽度的谱。中和效力和宽度进行了评估，与遗传和地理上不同的面板205慢性HIV-1血清和219 Env-假型病毒代表所有主要的HIV-1基因亚型。通过在TZM-bl细胞中使用Tat调节的荧光素酶报告基因表达来测量中和。将血清中和活性与广泛认为具有广泛中和性的一组不同的人mAb进行比较。我们观察到一致的连续反应，大多数血清表现出一定程度的交叉中和，大约50%的血清中和了超过50%的病毒。中和滴度（效价）与宽度高度相关。许多血清的宽度与几种效力较低的广泛中和人mAb相当。这些结果有助于澄清HIV-1感染诱导的血清中和活性谱，这应该是可能的疫苗。重要的是，大多数人似乎能够产生低至中等滴度的广泛中和抗体。对这些相对常见的反应的进一步研究可能为实际可行的疫苗设计提供见解。
Studies of neutralizing antibodies in HIV-1 infected individuals provide insights into the quality of the response that should be possible to elicit with vaccines and ways to design effective immunogens. Some individuals make high titres of exceptional broadly reactive neutralizing antibodies that are of particular interest; however, more modest responses may be a reasonable goal for vaccines. We performed a large cross-sectional study to determine the spectrum of neutralization potency and breadth that is seen during chronic HIV-1 infection. Neutralization potency and breadth were assessed with genetically and geographically diverse panels of 205 chronic HIV-1 sera and 219 Env-pseudotyped viruses representing all major genetic subtypes of HIV-1. Neutralization was measured by using Tat-regulated luciferase reporter gene expression in TZM-bl cells. Serum-neutralizing activity was compared with a diverse set of human mAbs that are widely considered to be broadly neutralizing. We observed a uniform continuum of responses, with most sera displaying some level of cross-neutralization, and approximately 50% of sera neutralizing more than 50% of viruses. Titres of neutralization (potency) were highly correlated with breadth. Many sera had breadth comparable to several of the less potent broadly neutralizing human mAbs. These results help clarify the spectrum of serum-neutralizing activity induced by HIV-1 infection and that should be possible to elicit with vaccines. Importantly, most people appear capable of making low to moderate titres of broadly neutralizing antibodies. Additional studies of these relatively common responses might provide insights for practical and feasible vaccine designs.