Early Antibody Lineage Diversification and Independent Limb Maturation Lead to Broad HIV-1 Neutralization Targeting the Env High-Mannose Patch.
Early Antibody Lineage Diversification and Independent Limb Maturation Lead to Broad HIV-1 Neutralization Targeting the Env High-Mannose Patch.
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DOI：
10.1016/j.immuni.2016.04.016
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发表时间：
2016-05-17
期刊：
影响因子：
32.4
通讯作者：
Poignard, Pascal
中科院分区：
文献类型：
--
作者：
MacLeod, Daniel T.;Choi, Nancy M.;Briney, Bryan;Garces, Fernando;Ver, Lorena S.;Landais, Elise;Murrell, Ben;Wrin, Terri;Kilembe, William;Liang, Chi-Hui;Ramos, Alejandra;Bian, Chaoran B.;Wickramasinghe, Lalinda;Kong, Leopold;Eren, Kemal;Wu, Chung-Yi;Wong, Chi-Huey;Pond, Sergei L. Kosakovsky;Wilson, Ian A.;Burton, Dennis R.;Poignard, Pascal
HIV Env上的高甘露糖斑块是广泛中和抗体（bnAb）的优选靶标，但迄今为止，没有疫苗接种方案引起针对该区域的bnAb。在这里，我们提出了一个bnAb谱系的发展，针对高甘露糖补丁在艾滋病毒-1亚型C感染的捐助者从撒哈拉以南非洲。Ab首先获得自体中和，然后逐渐成熟以实现宽度。一种Ab中和了>47%的HIV-1菌株，仅具有~11%的体细胞高突变，并且没有插入或缺失。通过对自体env进行测序，我们确定了触发谱系并参与Ab-Env共同进化的关键残基。下一代测序的抗体库显示了早期广泛的多样化的血统，随后独立的成熟的个别肢体，其中几个发展显着的广度和效力。总的来说，从疫苗的角度来看，这些发现是令人鼓舞的，并建议免疫策略模仿整个高甘露糖斑块的演变，并促进多种不同Ab途径的成熟。
The high-mannose patch on HIV Env is a preferred target for broadly neutralizing antibodies (bnAbs), but to date, no vaccination regimen has elicited bnAbs against this region. Here, we present the development of a bnAb lineage targeting the high-mannose patch in an HIV-1 subtype-C-infected donor from sub-Saharan Africa. The Abs first acquired autologous neutralization, then gradually matured to achieve breadth. One Ab neutralized >47% of HIV-1 strains with only ~11% somatic hypermutation and no insertions or deletions. By sequencing autologous env, we determined key residues that triggered the lineage and participated in Ab-Env coevolution. Next-generation sequencing of the Ab repertoire showed an early expansive diversification of the lineage followed by independent maturation of individual limbs, several of them developing notable breadth and potency. Overall, the findings are encouraging from a vaccine standpoint and suggest immunization strategies mimicking the evolution of the entire high-mannose patch and promoting maturation of multiple diverse Ab pathways.
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影响因子：
16.8
作者：
Kong, Leopold;Lee, Jeong Hyun;Doores, Katie J.;Murin, Charles D.;Julien, Jean-Philippe;McBride, Ryan;Liu, Yan;Marozsan, Andre;Cupo, Albert;Klasse, Per-Johan;Hoffenberg, Simon;Caulfield, Michael;King, C. Richter;Hua, Yuanzi;Le, Khoa M.;Khayat, Reza;Deller, Marc C.;Clayton, Thomas;Tien, Henry;Feizi, Ten;Sanders, Rogier W.;Paulson, James C.;Moore, John P.;Stanfield, Robyn L.;Burton, Dennis R.;Ward, Andrew B.;Wilson, Ian A.
通讯作者：
Wilson, Ian A.
影响因子：
32.4
作者：
Falkowska, Emilia;Le, Khoa M.;Ramos, Alejandra;Doores, Katie J.;Lee, Jeong Hyun;Blattner, Claudia;Ramirez, Alejandro;Derking, Ronald;van Gils, Marit J.;Liang, Chi-Hui;Mcbride, Ryan;von Bredow, Benjamin;Shivatare, Sachin S.;Wu, Chung-Yi;Chan-Hui, Po-Ying;Liu, Yan;Feizi, Ten;Zwick, Michael B.;Koff, Wayne C.;Seaman, Michael S.;Swiderek, Kristine;Moore, John P.;Evans, David;Paulson, James C.;Wong, Chi-Huey;Ward, Andrew B.;Wilson, Ian A.;Sanders, Rogier W.;Poignard, Pascal;Burton, Dennis R.
通讯作者：
Burton, Dennis R.
影响因子：
56.9
作者：
Haynes, BF;Fleming, J;Alam, SM
通讯作者：
Alam, SM
影响因子：
46.9
作者：
通讯作者：
--
影响因子：
64.8
作者：
Martin, A;Bardwell, PD;Scharff, MD
通讯作者：
Scharff, MD