Isolation of HIV-1-neutralizing mucosal monoclonal antibodies from human colostrum.
Isolation of HIV-1-neutralizing mucosal monoclonal antibodies from human colostrum.
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从人初乳中分离出 HIV-1 中和粘膜单克隆抗体。
DOI：
10.1371/journal.pone.0037648
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Permar SR
中科院分区：
文献类型：
--
作者：
Friedman J;Alam SM;Shen X;Xia SM;Stewart S;Anasti K;Pollara J;Fouda GG;Yang G;Kelsoe G;Ferrari G;Tomaras GD;Haynes BF;Liao HX;Moody MA;Permar SR
在粘膜隔室中产生有效的抗HIV抗体反应是传播阻断HIV疫苗的潜在要求。母乳中存在艾滋病毒特异性的功能性抗体反应，这些粘膜抗体反应可能对大多数艾滋病毒暴露的母乳喂养婴儿起保护作用。因此，鉴定牛奶中B细胞产生的hiv特异性抗体可以指导疫苗的开发，从而引发保护性粘膜抗体反应。我们从一名感染hiv的哺乳期妇女的初乳中分离出B细胞，并重组产生了HIV-1包膜（Env）特异性单克隆抗体（mab）。鉴定出的HIV-1 env特异性初乳单克隆抗体CH07和CH08是目前尚未报道的两种最早的粘膜来源的抗hiv抗体。初乳单抗CH07是一种高自反应性、弱中和的gp140特异性单抗，可结合gp120 C5区域和gp41融合域的线性表位。相比之下，初乳单抗CH08是一种非多反应性cd4诱导（CD4i）的gp120特异性单抗，具有中等的中和宽度。这些从粘膜隔室分离的新型hiv中和单克隆抗体提供了对粘膜B细胞群产生功能性抗hiv抗体的能力的深入了解，这种抗体可能有助于防止粘膜表面的病毒获得。
Generation of potent anti-HIV antibody responses in mucosal compartments is a potential requirement of a transmission-blocking HIV vaccine. HIV-specific, functional antibody responses are present in breast milk, and these mucosal antibody responses may play a role in protection of the majority of HIV-exposed, breastfeeding infants. Therefore, characterization of HIV-specific antibodies produced by B cells in milk could guide the development of vaccines that elicit protective mucosal antibody responses. We isolated B cells from colostrum of an HIV-infected lactating woman with a detectable neutralization response in milk and recombinantly produced and characterized the resulting HIV-1 Envelope (Env)-specific monoclonal antibodies (mAbs). The identified HIV-1 Env-specific colostrum mAbs, CH07 and CH08, represent two of the first mucosally-derived anti-HIV antibodies yet to be reported. Colostrum mAb CH07 is a highly-autoreactive, weakly-neutralizing gp140-specific mAb that binds to linear epitopes in the gp120 C5 region and gp41 fusion domain. In contrast, colostrum mAb CH08 is a nonpolyreactive CD4-inducible (CD4i) gp120-specific mAb with moderate breadth of neutralization. These novel HIV-neutralizing mAbs isolated from a mucosal compartment provide insight into the ability of mucosal B cell populations to produce functional anti-HIV antibodies that may contribute to protection against virus acquisition at mucosal surfaces.
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