Immunization for HIV-1 Broadly Neutralizing Antibodies in Human Ig Knockin Mice.
Immunization for HIV-1 Broadly Neutralizing Antibodies in Human Ig Knockin Mice.
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DOI：
10.1016/j.cell.2015.06.003
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发表时间：
2015-06-18
期刊：
影响因子：
64.5
通讯作者：
Nussenzweig MC
中科院分区：
文献类型：
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作者：
Dosenovic P;von Boehmer L;Escolano A;Jardine J;Freund NT;Gitlin AD;McGuire AT;Kulp DW;Oliveira T;Scharf L;Pietzsch J;Gray MD;Cupo A;van Gils MJ;Yao KH;Liu C;Gazumyan A;Seaman MS;Björkman PJ;Sanders RW;Moore JP;Stamatatos L;Schief WR;Nussenzweig MC
A subset of individuals infected with human immunodeficiency virus 1 (HIV-1) develops broadly neutralizing antibodies (bNAbs) that can prevent infection, but it has not yet been possible to elicit these antibodies by immunization. To systematically explore how immunization might be tailored to produce them, we generated mice expressing a diverse repertoire of light chains and predicted germline or mature heavy chains of a potent bNAb to the CD4 binding site (CD4bs) on the HIV-1 envelope glycoprotein (Env). Immunogens specifically designed to activate B cells bearing germline antibodies are required to initiate immune responses, but they do not elicit bNAbs. In contrast, native-like Env trimers fail to activate B cells expressing germline antibodies but elicit bNAbs by selecting for a restricted group of light chains bearing specific somatic mutations that enhance neutralizing activity. The data suggest that vaccination to elicit anti-HIV-1 antibodies will require immunization with a succession of related immunogens.
