Anti-idiotypic antibodies elicit anti-HIV-1-specific B cell responses
Anti-idiotypic antibodies elicit anti-HIV-1-specific B cell responses
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DOI：
10.1084/jem.20190446
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发表时间：
2019-10-01
影响因子：
15.3
通讯作者：
McGuire, Andrew T.
中科院分区：
文献类型：
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作者：
Dosenovic, Pia;Pettersson, Anna-Klara;McGuire, Andrew T.
人类抗hiv -1广泛中和抗体（bNAbs）在动物模型中保护免受感染。然而，在多种野生型动物或人类中，bNAbs并没有通过接种引起，部分原因是表达这些抗体前体的B细胞不能识别大多数HIV-1包膜（Envs）。免疫原已经被设计成在体内激活这些B细胞前体，但它们也会激活竞争性的脱靶反应。在这里，我们报道了一种利用抗独特型抗体iv8扩增特异性B细胞的互补方法，该抗体选择表达具有5个氨基酸互补决定区3s的免疫球蛋白轻链的幼稚人B细胞，这是抗cd4结合位点（CD4bs）特异性vrc01类抗体的关键特征。在小鼠实验中，iv8在多克隆免疫系统环境下诱导靶细胞扩增和成熟，并产生针对Env上CD4bs的血清学应答。综上所述，抗独特型抗体可以特异性识别和扩增表达vrc01类抗HIV-1抗体的罕见B细胞。
Human anti-HIV-1 broadly neutralizing antibodies (bNAbs) protect against infection in animal models. However, bNAbs have not been elicited by vaccination in diverse wild-type animals or humans, in part because B cells expressing the precursors of these antibodies do not recognize most HIV-1 envelopes (Envs). Immunogens have been designed that activate these B cell precursors in vivo, but they also activate competing off-target responses. Here we report on a complementary approach to expand specific B cells using an anti-idiotypic antibody, iv8, that selects for naive human B cells expressing immunoglobulin light chains with 5-amino acid complementarity determining region 3s, a key feature of anti-CD4 binding site (CD4bs)-specific VRC01-class antibodies. In mice, iv8 induced target cells to expand and mature in the context of a polyclonal immune system and produced serologic responses targeting the CD4bs on Env. In summary, the results demonstrate that an anti-idiotypic antibody can specifically recognize and expand rare B cells that express VRC01-class antibodies against HIV-1.