Mucosal and Vaccine Research Colorado (MAVRC), University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Denver Veterans Affairs Medical Center, Denver, CO 80220, USA.
Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
J Infect. 2014 Mar;68(3):264-72. doi: 10.1016/j.jinf.2013.11.002. Epub 2013 Nov 13.
Among HIV-exposed infants in resource-limited countries, 8-12% are infected postnatally by breastfeeding. However, most of those uninfected at birth remain uninfected over time despite daily exposure to HIV in breast milk. Thus, we assessed the HIV-inhibitory activity of breast milk.
We measured cross-clade neutralization in activated PBMC of Ugandan subtype A (92UG031) and D (92UG005) primary HIV by breast milk or purified milk IgG and IgA from 25 HIV-infected Ugandan women. Isotype-specific antigen recognition was resolved by immunoblot. We determined HIV subtype from envelope population sequences in cells from 13 milk samples by PCR.
Milk inhibited p24 production by ≥50% (dose-dependent) by subtype A (21/25; 84%) and subtype D (11/25; 44%). IgG consistently reacted with multiple HIV antigens, including gp120/gp41, but IgA primarily recognized p24 alone. Depletion of IgG (n = 5), not IgA, diminished neutralization (mean 78 ± 33%) that was largely restored by IgG repletion. Mothers infected with subtype A more effectively neutralized subtype A than D.
Breast milk from HIV-infected women showed homotypic and cross-subtype neutralization of HIV by IgG-dependent and -independent mechanisms. These data direct further investigations into mechanisms of resistance against postnatal transmission of HIV to infants from their mothers.
在资源有限的国家中，8-12%的 HIV 暴露婴儿会在产后通过母乳喂养而感染。然而，大多数在出生时未感染的婴儿尽管每天都接触母乳中的 HIV，但随着时间的推移仍能保持未感染状态。因此，我们评估了母乳的 HIV 抑制活性。
我们通过测量来自 25 名感染 HIV 的乌干达妇女的母乳或纯化的牛奶 IgG 和 IgA 对来自乌干达 A 亚型（92UG031）和 D 亚型（92UG005）的原发性 HIV 在激活的 PBMC 中的跨型中和作用，来评估 HIV 抑制活性。通过免疫印迹法确定了特异性同种型的抗原识别。我们通过 PCR 从 13 个母乳样本中的细胞中确定了 HIV 亚型的包膜种群序列。
牛奶对 A 亚型（21/25；84%）和 D 亚型（11/25；44%）均表现出抑制 p24 产生≥50%（剂量依赖性）的效果。IgG 始终与多种 HIV 抗原反应，包括 gp120/gp41，但 IgA 主要单独识别 p24。耗尽 IgG（n=5）而不是 IgA 会降低中和作用（平均 78±33%），而 IgG 的补充则在很大程度上恢复了中和作用。感染 A 亚型的母亲对 A 亚型的中和作用比 D 亚型更有效。
来自感染 HIV 的女性的母乳通过 IgG 依赖性和非依赖性机制显示出对 HIV 的同源和跨型中和作用。这些数据为进一步研究针对母婴垂直传播的 HIV 感染的抵抗机制提供了方向。
