美國(guó)杜克大學(xué)醫(yī)學(xué)中心研究人員發(fā)現(xiàn)了兩種強(qiáng)力抗體——2F5和4E10阻斷艾滋病病毒（HIV）感染的機(jī)制,。該發(fā)現(xiàn)為研制新的,、更有效的艾滋病疫苗指出了一個(gè)新方向。相關(guān)研究刊發(fā)在《美國(guó)國(guó)家科學(xué)院院刊》上,。
美國(guó)杜克大學(xué)醫(yī)學(xué)中心人類疫苗研究所的S·穆尼爾·阿拉姆博士和哈佛醫(yī)學(xué)院的兒科助理教授陳兵（音譯）博士一起,，對(duì)兩種對(duì)抗HIV的潛在強(qiáng)力抗體——2F5和4E10進(jìn)行了研究。這兩種抗體十分罕見,，屬于廣效性中和抗體,，它們能夠阻斷若干不同的HIV毒株。HIV有其致命的薄弱之處,，即所謂的病毒外層包膜近側(cè)區(qū),。在這一區(qū)域靠近病毒包膜的一部分外蛋白質(zhì)層，會(huì)在細(xì)胞融合和感染過程中短暫開放,，從而使病毒有幾分鐘的時(shí)間暴露在抗體面前,。而這兩種抗體正是利用這個(gè)機(jī)會(huì)與病毒綁定，從而阻斷HIV,。
但要控制病毒感染,，還面臨著這樣的問題：在艾滋病病毒感染者中，這兩種抗體十分罕見,，而目前的試驗(yàn)性疫苗還不能產(chǎn)生這些抗體,。此外，這類抗體的“機(jī)會(huì)之窗”也十分狹窄,。
“病毒目標(biāo)區(qū)域只開放幾分鐘——也許只有15分鐘甚至更短,。”阿拉姆博士說(shuō)，“除非抗體與目標(biāo)十分接近,，并做好了準(zhǔn)備,，否則就不會(huì)起作用,。這意味著我們要設(shè)計(jì)出新型疫苗，可誘導(dǎo)更多的這類抗體,，讓它們?cè)诟腥镜淖畛蹼A段即投入戰(zhàn)斗,。”
2F5和4E10都具有很長(zhǎng)的、一圈一圈的蛋白質(zhì)片段,，這些片段具有疏水性,，這意味著它們?nèi)菀妆恢|(zhì)吸引。研究人員發(fā)現(xiàn),，抗體要成功對(duì)接到HIV的外膜區(qū)域,，有賴于抗體可依附在HIV外層類脂包膜上，而這些包膜中就含有脂質(zhì),。
該研究團(tuán)隊(duì)已開始設(shè)計(jì)一種含有脂質(zhì)成分的疫苗,。該論文的合著者、人類疫苗研究所主任巴頓·海恩斯指出,，在這些中和抗體的所有功能中，病毒粒子脂質(zhì)反應(yīng)性作用給他們的研究提供了一個(gè)關(guān)鍵性切入點(diǎn),，即免疫系統(tǒng)需要看到什么才會(huì)產(chǎn)生這類抗體。他們基于這些發(fā)現(xiàn)而設(shè)計(jì)出的新型疫苗,，目前已開始進(jìn)行動(dòng)物試驗(yàn),。（生物谷Bioon.com）
生物谷推薦原始出處：
PNAS November 11, 2009, doi: 10.1073/pnas.0908713106
Role of HIV membrane in neutralization by two broadly neutralizing antibodies
S. Munir Alama,1,2, Marco Morellib,c,1, S. Moses Dennisona, Hua-Xin Liaoa, Ruijun Zhanga, Shi-Mao Xiaa, Sophia Rits-Vollochb,d, Li Sune, Stephen C. Harrisona,d,f, Barton F. Haynesa and Bing Chenb,f,2
aHuman Vaccine Institute, Duke University School of Medicine, Durham, NC 27710;
bLaboratory of Molecular Medicine, Children's Hospital,
dHoward Hughes Medical Institute, and
fDepartment of Pediatrics, Harvard Medical School, 320 Longwood Avenue, Boston, MA 02115;
cProgram in Virology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115; and
eXiamen Amoytop Biotech Company, Ltd., 330 Wengjiao Road, Xiamen, Fujian, China 361022
Induction of effective antibody responses against HIV-1 infection remains an elusive goal for vaccine development. Progress may require in-depth understanding of the molecular mechanisms of neutralization by monoclonal antibodies. We have analyzed the molecular actions of two rare, broadly neutralizing, human monoclonal antibodies, 4E10 and 2F5, which target the transiently exposed epitopes in the membrane proximal external region (MPER) of HIV-1 gp41 envelope during viral entry. Both have long CDR H3 loops with a hydrophobic surface facing away from the peptide epitope. We find that the hydrophobic residues of 4E10 mediate a reversible attachment to the viral membrane and that they are essential for neutralization, but not for interaction with gp41. We propose that these antibodies associate with the viral membrane in a required first step and are thereby poised to capture the transient gp41 fusion intermediate. These results bear directly on strategies for rational design of HIV-1 envelope immunogens.
