PLoS ONE：人初乳中分离出HIV-1单克隆抗体

近日，来自美国杜克大学医学中心的研究人员表示，他们在人初乳中得到能够中和HIV-1的黏膜单克隆抗体。相关研究成果于5月18日发表在PLoS ONE上。

在黏膜间隙能够产生有效的抗HIV反应，是发展HIV疫苗的一个潜在需求。在母乳中发现了HIV特异性的功能性抗体反应后，Sallie R. Permar表示，这些抗体反应可能对保护由母乳喂养的HIV暴露婴儿具有重要作用。因此，研究乳汁中由B细胞产生的HIV特异性抗体，利于引导科研工作者发展能够引起保护性黏膜抗体反应的疫苗。

在研究过程中，他们利用乳汁中可检测到的中和反应，分离了携带HIV的泌乳妇女初乳中的B细胞。随后，他们得到了HIV-1包膜(Env)特异性的单克隆抗体(mAbs)。

已鉴定的初乳中HIV-1包膜特异性单克隆抗体有CH07和CH08，它们是首次发现的两种黏膜衍生的抗HIV抗体。

CH07是一种能够高度自身反应，中和作用较弱的gp140特异性单克隆抗体，它主要结合到在gp120 C5区及gp41融合结构域的线性抗原。

与此相反，CH08是一种‘非多反应性’的CD4可诱导的(CD4i)gp120特异性单克隆抗体，具有适度的中和能力。

该研究表明，黏膜相关性B细胞能够产生功能性抗HIV抗体，在黏膜表面防御病毒入侵。（生物谷Deepblue编译）

doi: 10.1371/journal.pone.0037648
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Isolation of HIV-1-Neutralizing Mucosal Monoclonal Antibodies from Human Colostrum

James Friedman, S. Munir Alam, Xiaoying Shen, Shi-Mao Xia, Shelley Stewart, Kara Anasti, Justin Pollara, Genevieve G. Fouda, Guang Yang, Garnett Kelsoe, Guido Ferrari, Georgia D. Tomaras, Barton F. Haynes, Hua-Xin Liao, M. Anthony Moody, Sallie R. Permar.

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.