Broad neutralization by a combination of antibodies recognizing the CD4 binding site and a new conformational epitope on the HIV-1 envelope protein.
Broad neutralization by a combination of antibodies recognizing the CD4 binding site and a new conformational epitope on the HIV-1 envelope protein.
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DOI：
10.1084/jem.20120423
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发表时间：
2012-07-30
期刊：
影响因子：
--
通讯作者：
Nussenzweig MC
中科院分区：
文献类型：
--
作者：
Klein F;Gaebler C;Mouquet H;Sather DN;Lehmann C;Scheid JF;Kraft Z;Liu Y;Pietzsch J;Hurley A;Poignard P;Feizi T;Morris L;Walker BD;Fätkenheuer G;Seaman MS;Stamatatos L;Nussenzweig MC
一种新的方法用于分离中和抗体，识别细胞表面表达但不可溶的HIV-1刺突上的新表位。感染后2 - 3年，一部分HIV-1感染者会产生血清学活性，中和大多数病毒分离株。通过单细胞分选和中和筛选，已从这些患者中分离出识别HIV-1包膜蛋白的广泛中和抗体。在这里，我们报告了一种新的方法，抗HIV-1抗体分离的基础上捕获单个B细胞，识别HIV-1包膜蛋白表达的转染细胞的表面上。尽管远不如可溶性蛋白诱饵有效，但基于细胞的捕获方法鉴定了与V3环和CD 4诱导位点（CD 4 i）附近的新的广泛中和表位结合的抗体。新的表位在HIV-1刺突的细胞表面形式上表达，但不在相同包膜蛋白的可溶形式上表达。此外，新抗体补充了从同一个体获得的强效广泛中和抗CD 4结合位点（CD 4 bs）抗体的中和谱。因此，具有互补活性的有效广泛中和抗体的组合可以解释天然产生的抗HIV-1血清学活性的广度和效力。因此，旨在引发抗HIV-1血清学广度和效力的疫苗不应限于单一表位。
A new method is used to isolate neutralizing antibodies recognizing a new epitope on the cell surface–expressed, but not soluble, HIV-1 spike. Two to three years after infection, a fraction of HIV-1–infected individuals develop serologic activity that neutralizes most viral isolates. Broadly neutralizing antibodies that recognize the HIV-1 envelope protein have been isolated from these patients by single-cell sorting and by neutralization screens. Here, we report a new method for anti–HIV-1 antibody isolation based on capturing single B cells that recognize the HIV-1 envelope protein expressed on the surface of transfected cells. Although far less efficient than soluble protein baits, the cell-based capture method identified antibodies that bind to a new broadly neutralizing epitope in the vicinity of the V3 loop and the CD4-induced site (CD4i). The new epitope is expressed on the cell surface form of the HIV-1 spike, but not on soluble forms of the same envelope protein. Moreover, the new antibodies complement the neutralization spectrum of potent broadly neutralizing anti-CD4 binding site (CD4bs) antibodies obtained from the same individual. Thus, combinations of potent broadly neutralizing antibodies with complementary activity can account for the breadth and potency of naturally arising anti–HIV-1 serologic activity. Therefore, vaccines aimed at eliciting anti–HIV-1 serologic breadth and potency should not be limited to single epitopes.
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影响因子：
3.7
作者：
Corti D;Langedijk JP;Hinz A;Seaman MS;Vanzetta F;Fernandez-Rodriguez BM;Silacci C;Pinna D;Jarrossay D;Balla-Jhagjhoorsingh S;Willems B;Zekveld MJ;Dreja H;O'Sullivan E;Pade C;Orkin C;Jeffs SA;Montefiori DC;Davis D;Weissenhorn W;McKnight A;Heeney JL;Sallusto F;Sattentau QJ;Weiss RA;Lanzavecchia A
通讯作者：
Lanzavecchia A
影响因子：
56.9
作者：
BURTON, DR;PYATI, J;BARBAS, CF
通讯作者：
BARBAS, CF
影响因子：
5.4
作者：
Gorny, MK;Stamatatos, L;Zolla-Pazner, S
通讯作者：
Zolla-Pazner, S
影响因子：
3.7
作者：
Morris L;Chen X;Alam M;Tomaras G;Zhang R;Marshall DJ;Chen B;Parks R;Foulger A;Jaeger F;Donathan M;Bilska M;Gray ES;Abdool Karim SS;Kepler TB;Whitesides J;Montefiori D;Moody MA;Liao HX;Haynes BF
通讯作者：
Haynes BF
影响因子：
6.7
作者：
Mikell I;Sather DN;Kalams SA;Altfeld M;Alter G;Stamatatos L
通讯作者：
Stamatatos L