近日，來(lái)自美國(guó)杜克大學(xué)醫(yī)學(xué)中心的研究人員表示,，他們?cè)谌顺跞橹械玫侥軌蛑泻虷IV-1的黏膜單克隆抗體,。相關(guān)研究成果于5月18日發(fā)表在PLoS ONE上。
在黏膜間隙能夠產(chǎn)生有效的抗HIV反應(yīng),，是發(fā)展HIV疫苗的一個(gè)潛在需求,。在母乳中發(fā)現(xiàn)了HIV特異性的功能性抗體反應(yīng)后，Sallie R. Permar表示,，這些抗體反應(yīng)可能對(duì)保護(hù)由母乳喂養(yǎng)的HIV暴露嬰兒具有重要作用,。因此，研究乳汁中由B細(xì)胞產(chǎn)生的HIV特異性抗體,，利于引導(dǎo)科研工作者發(fā)展能夠引起保護(hù)性黏膜抗體反應(yīng)的疫苗,。
在研究過(guò)程中，他們利用乳汁中可檢測(cè)到的中和反應(yīng),，分離了攜帶HIV的泌乳婦女初乳中的B細(xì)胞,。隨后，他們得到了HIV-1包膜(Env)特異性的單克隆抗體(mAbs),。
已鑒定的初乳中HIV-1包膜特異性單克隆抗體有CH07和CH08,，它們是首次發(fā)現(xiàn)的兩種黏膜衍生的抗HIV抗體。
CH07是一種能夠高度自身反應(yīng),，中和作用較弱的gp140特異性單克隆抗體,，它主要結(jié)合到在gp120 C5區(qū)及gp41融合結(jié)構(gòu)域的線性抗原。
與此相反,，CH08是一種‘非多反應(yīng)性’的CD4可誘導(dǎo)的(CD4i)gp120特異性單克隆抗體,，具有適度的中和能力。
該研究表明,，黏膜相關(guān)性B細(xì)胞能夠產(chǎn)生功能性抗HIV抗體,，在黏膜表面防御病毒入侵。（生物谷Deepblue編譯）
doi: 10.1371/journal.pone.0037648
PMC:
PMID:
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.
