AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan ; The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
PLoS One. 2013 Sep 9;8(9):e73453. doi: 10.1371/journal.pone.0073453. eCollection 2013.
Antiviral antibodies, especially those with neutralizing activity against the incoming strain, are potentially important immunological effectors to control human immunodeficiency virus (HIV) infection. While neutralizing activity appears to be central in sterile protection against HIV infection, the entity of inhibitory mechanisms via HIV and simian immunodeficiency virus (SIV)-specific antibodies remains elusive. The recent HIV vaccine trial RV144 and studies in nonhuman primate models have indicated controversial protective efficacy of HIV/SIV-specific non-neutralizing binding antibodies (non-NAbs). While reports on HIV-specific non-NAbs have demonstrated virus inhibitory activity in vitro, whether non-NAbs could also alter the pathogenic course of established SIV replication in vivo, likewise via neutralizing antibody (NAb) administration, has been unclear. Here, we performed post-infection passive immunization of SIV-infected rhesus macaques with polyclonal SIV-specific, antibody-dependent cell-mediated viral inhibition (ADCVI)-competent non-NAbs.
Ten lots of polyclonal immunoglobulin G (IgG) were prepared from plasma of ten chronically SIVmac239-infected, NAb-negative rhesus macaques, respectively. Their binding capacity to whole SIVmac239 virions showed a propensity similar to ADCVI activity. A cocktail of three non-NAb lots showing high virion-binding capacity and ADCVI activity was administered to rhesus macaques at day 7 post-SIVmac239 challenge. This resulted in an infection course comparable with control animals, with no significant difference in set point plasma viral loads or immune parameters.
Despite virus-specific suppressive activity of the non-NAbs having been observed in vitro, their passive immunization post-infection did not result in SIV control in vivo. Virion binding and ADCVI activity with lack of virus neutralizing activity were indicated to be insufficient for antibody-triggered non-sterile SIV control. More diverse effector functions or sophisticated localization may be required for non-NAbs to impact HIV/SIV replication in vivo.
抗病毒抗体，特别是针对传入株具有中和活性的抗体，是控制人类免疫缺陷病毒（HIV）感染的潜在重要免疫效应物。虽然中和活性似乎是对抗 HIV 感染的无菌保护的核心，但 HIV 和猴免疫缺陷病毒（SIV）特异性抗体的抑制机制的实体仍然难以捉摸。最近的 HIV 疫苗试验 RV144 和非人类灵长类动物模型的研究表明，HIV/SIV 特异性非中和结合抗体（非中和抗体）的保护效果存在争议。虽然关于 HIV 特异性非中和抗体的报告表明，在体外具有病毒抑制活性，但非中和抗体是否也可以通过中和抗体（NAb）给药来改变体内已建立的 SIV 复制的发病过程，同样不清楚。在这里，我们通过感染 SIV 的恒河猴进行感染后被动免疫，用多克隆 SIV 特异性、抗体依赖性细胞介导的病毒抑制（ADCVI）活性的非中和抗体。
从 10 只慢性 SIVmac239 感染、NAb 阴性恒河猴的血浆中分别制备了 10 份多克隆免疫球蛋白 G（IgG）。它们与整个 SIVmac239 病毒粒子的结合能力显示出类似于 ADCVI 活性的倾向。三批具有高病毒粒子结合能力和 ADCVI 活性的非中和抗体混合物在 SIVmac239 攻击后第 7 天给予恒河猴。这导致感染过程与对照动物相当，在设定点血浆病毒载量或免疫参数方面没有显著差异。
尽管已经在体外观察到非中和抗体的病毒特异性抑制活性，但它们在感染后的被动免疫并没有导致体内 SIV 的控制。表明缺乏病毒中和活性的病毒粒子结合和 ADCVI 活性不足以触发非无菌的 SIV 控制。非中和抗体要在体内影响 HIV/SIV 复制，可能需要更多的效应功能或复杂的定位。
