Developmental pathway for potent V1V2-directed HIV-neutralizing antibodies.
Developmental pathway for potent V1V2-directed HIV-neutralizing antibodies.
复制标题
有效V1V2定向HIV中和抗体的发育途径。
DOI：
10.1038/nature13036
复制
发表时间：
2014-05-01
期刊：
影响因子：
64.8
通讯作者：
Mascola, John R.
中科院分区：
文献类型：
--
作者：
Doria-Rose, Nicole A.;Schramm, Chaim A.;Gorman, Jason;Moore, Penny L.;Bhiman, Jinal N.;DeKosky, Brandon J.;Ernandes, Michael J.;Georgiev, Ivelin S.;Kim, Helen J.;Pancera, Marie;Staupe, Ryan P.;Altae-Tran, Han R.;Bailer, Robert T.;Crooks, Ema T.;Cupo, Albert;Druz, Aliaksandr;Garrett, Nigel J.;Hoi, Kam H.;Kong, Rui;Louder, Mark K.;Longo, Nancy S.;McKee, Krisha;Nonyane, Molati;O'Dell, Sijy;Roark, Ryan S.;Rudicell, Rebecca S.;Schmidt, Stephen D.;Sheward, Daniel J.;Soto, Cinque;Wibmer, Constantinos Kurt;Yang, Yongping;Zhang, Zhenhai;Mullikin, James C.;Binley, James M.;Sanders, Rogier W.;Wilson, Ian A.;Moore, John P.;Ward, Andrew B.;Georgiou, George;Williamson, Carolyn;Karim, Salim S. Abdool;Morris, Lynn;Kwong, Peter D.;Shapiro, Lawrence;Mascola, John R.
能够中和 HIV-1 的抗体通常靶向 HIV-1 包膜的可变区 1 和 2 (V1V2)，但其引发机制尚不清楚。在这里，我们定义了产生此类抗体并获得中和所需的分子特征的发育途径。从 CAPRISA 供体 CAP256 中分离出 12 种体细胞相关的中和抗体 (CAP256-VRC26.01-12)；每种抗体均含有此类抗体特有的突出酪氨酸硫酸化阴离子抗原结合环 (CDR H3)。他们的未突变祖先在感染后 30-38 周内出现，带有 35 个残基的 CDR H3，并在初次感染后 15 周中和了对该个体进行重复感染的病毒。中和广度在第 59 周时出现改善，亲和力适度成熟，在此之前病毒种群广泛多样化。因此，通过对具有长 CDR H3 的 B 细胞进行初始选择，HIV-1 V1V2 定向的中和抗体可以相对快速地发展，并限制随后的体细胞超突变，这是一个重要的疫苗见解。
Antibodies capable of neutralizing HIV-1 often target variable regions 1 and 2 (V1V2) of the HIV-1 envelope, but the mechanism of their elicitation has been unclear. Here we define the developmental pathway by which such antibodies are generated and acquire the requisite molecular characteristics for neutralization. Twelve somatically related neutralizing antibodies (CAP256-VRC26.01-12) were isolated from CAPRISA-donor CAP256; each antibody contained the protruding tyrosine-sulfated, anionic antigen-binding loop (CDR H3) characteristic of this category of antibodies. Their unmutated ancestor emerged between weeks 30–38 post-infection with a 35-residue CDR H3, and neutralized the virus that superinfected this individual 15 weeks after initial infection. Improved neutralization breadth occurred by week 59 with modest affinity maturation, and was preceded by extensive diversification of the virus population. HIV-1 V1V2-directed neutralizing antibodies can thus develop relatively rapidly through initial selection of B cells with a long CDR H3, and limited subsequent somatic hypermutation, an important vaccine insight.
登录
查看更多内容
影响因子：
64.8
作者：
Huang J;Ofek G;Laub L;Louder MK;Doria-Rose NA;Longo NS;Imamichi H;Bailer RT;Chakrabarti B;Sharma SK;Alam SM;Wang T;Yang Y;Zhang B;Migueles SA;Wyatt R;Haynes BF;Kwong PD;Mascola JR;Connors M
通讯作者：
Connors M
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：
--
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
3.7
作者：
Briney BS;Willis JR;Crowe JE Jr
通讯作者：
Crowe JE Jr