Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Boston, MA, USA.
Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Australia.
AIDS. 2018 Jun 19;32(10):1207-1217. doi: 10.1097/QAD.0000000000001812.
Postinfection HIV viral control and immune correlates analysis of the RV144 vaccine trial indicate a potentially critical role for Fc receptor-mediated antibody functions. However, the influence of functional antibodies in clade C infection is largely unknown.
Plasma samples from 361 chronic subtype C-infected, antiretroviral therapy-naive participants were tested for their HIV-specific isotype and subclass distributions, along with their Fc receptor-mediated functional potential.
Total IgG, IgG subclasses and IgA binding to p24 clade B/C and gp120 consensus C proteins were assayed by multiplex. Antibody-dependent uptake of antigen-coated beads and Fc receptor-mediated natural killer cell degranulation were evaluated as surrogates for antibody-dependent cellular phagocytosis (ADCP) and antibody-dependent cellular cytotoxicity (ADCC), respectively.
p24 IgG1 was the only subclass associated with viral control (P = 0.01), with higher p24-specific ADCP and ADCC responses detected in individuals with high p24 IgG1. Although p24 IgG1 levels were enriched in patients with elevated Gag-specific T-cell responses, these levels remained an independent predictor of low-viral loads (P = 0.04) and high CD4+ cell counts (P = 0.004) after adjusting for Gag-specific T-cell responses and for protective HLA class I alleles.
p24 IgG1 levels independently predict viral control in HIV-1 clade C infection. Whether these responses contribute to direct antiviral control via the recruited killing of infected cells via the innate immune system or simply mark a qualitatively superior immune response to HIV, is uncertain, but highlights the role of p24-specific antibodies in control of clade C HIV-1 infection.
RV144 疫苗试验的感染后 HIV 病毒控制和免疫相关性分析表明，Fc 受体介导的抗体功能可能起着至关重要的作用。然而，功能抗体在 C 型病毒感染中的影响在很大程度上尚不清楚。
对 361 例慢性 C 型感染、未接受抗逆转录病毒治疗的参与者的血浆样本进行 HIV 特异性同种型和亚类分布检测，以及 Fc 受体介导的功能潜力检测。
通过多重分析检测 p24 型 B/C 和 gp120 型 C 共有蛋白的总 IgG、IgG 亚类和 IgA 结合情况。评估抗体依赖性摄取包被抗原珠和 Fc 受体介导的自然杀伤细胞脱颗粒作为抗体依赖性细胞吞噬（ADCP）和抗体依赖性细胞细胞毒性（ADCC）的替代物。
p24 IgG1 是唯一与病毒控制相关的亚类（P=0.01），在 p24 特异性 ADCP 和 ADCC 反应较高的个体中检测到更高的 p24 特异性 ADCP 和 ADCC 反应。尽管 p24 IgG1 水平在 Gag 特异性 T 细胞反应升高的患者中丰富，但这些水平在调整 Gag 特异性 T 细胞反应和保护性 HLA Ⅰ类等位基因后，仍然是低病毒载量（P=0.04）和高 CD4+细胞计数（P=0.004）的独立预测因子。
p24 IgG1 水平独立预测 HIV-1 C 型感染中的病毒控制。这些反应是否通过先天免疫系统募集杀伤感染细胞来直接抗病毒控制，或者只是标志着对 HIV 的质量更高的免疫反应尚不确定，但强调了 p24 特异性抗体在控制 C 型 HIV-1 感染中的作用。
