Division of Infectious Diseases, Department of Medicine, University of California, Irvine School of Medicine, USA.
AIDS. 2011 Nov 13;25(17):2099-104. doi: 10.1097/QAD.0b013e32834b64bd.
To determine the effect of IgG2 opsonization on internalization of HIV-1 virus-like particles (VLPs) by monocytes and to determine the effect of gp120 glycosylation on IgG subclass binding.
Fc-Fcγ receptor (FcγR) interactions are important in antibody-mediated protection from lentivirus infection. Such interactions are influenced by IgG subclass, with IgG2 having low affinity to most FcγRs. We determined the impact of IgG2 on internalization of antibody-opsonized VLPs. It is also known that gp120 glycans affect the binding and function of anti-gp120 antibodies. We determined whether binding of each IgG subclass to recombinant gp120 (rgp120) was similarly impacted by gp120 glycosylation.
Green fluorescent protein (GFP) containing VLPs were opsonized with IgG and IgG2-depleted IgG from individuals vaccinated with rgp120 during the Vax004 vaccine trial. Opsonized VLPs were incubated with peripheral blood mononuclear cells from healthy donors (n = 46), and percentages of GFP+ monocytes were determined by flow cytometry. IgG subclass binding of pooled and individual sera to rgp120 and to deglycosylated (PNGase-treated) rgp120 was determined by ELISA.
IgG2 elicited by rgp120 vaccination inhibited internalization of antibody-opsonized HIV-1 VLPs by monocytes from healthy individuals (P = 2.8 × 10(-5)). We also found that both IgG2 and IgG4 bound more poorly to enzymatically deglycosylated rgp120 than to unchanged rgp120. On the contrary, IgG1 and IgG3 bound slightly better to deglycosylated rgp120.
Vaccine-induced IgG2 may adversely affect a potentially important antiviral antibody activity, and altering Env glycans might provide the means to bias the subclass response in a favorable direction.
确定 IgG2 调理作用对单核细胞内化 HIV-1 病毒样颗粒（VLPs）的影响，并确定 gp120 糖基化对 IgG 亚类结合的影响。
Fc-Fcγ 受体（FcγR）相互作用对于抗体介导的抗慢病毒感染至关重要。这种相互作用受 IgG 亚类影响，IgG2 对大多数 FcγR 的亲和力较低。我们确定了 IgG2 对抗体调理的 VLP 内化的影响。已知 gp120 聚糖会影响抗 gp120 抗体的结合和功能。我们确定每个 IgG 亚类与重组 gp120（rgp120）的结合是否受到 gp120 糖基化的类似影响。
用 Vax004 疫苗试验中接种 rgp120 的个体的 IgG 和 IgG2 耗尽 IgG 对含 GFP 的 VLP 进行调理。用健康供体的外周血单核细胞（n = 46）孵育调理后的 VLP，并通过流式细胞术确定 GFP+单核细胞的百分比。通过 ELISA 确定Pooled 和个体血清与 rgp120 和去糖基化（PNGase 处理）的 rgp120 的 IgG 亚类结合。
rgp120 疫苗接种引起的 IgG2 抑制了来自健康个体单核细胞内化抗体调理的 HIV-1 VLP（P = 2.8×10(-5)）。我们还发现，与未改变的 rgp120 相比，IgG2 和 IgG4 与酶促去糖基化的 rgp120 的结合能力较差。相反，IgG1 和 IgG3 与去糖基化的 rgp120 的结合能力略有提高。
疫苗诱导的 IgG2 可能会对一种潜在的重要抗病毒抗体活性产生不利影响，而改变Env 聚糖可能为朝着有利方向偏向亚类反应提供手段。
