Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA.
Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA.
J Exp Med. 2019 Oct 7;216(10):2331-2347. doi: 10.1084/jem.20190164. Epub 2019 Jul 25.
Many tested vaccines fail to provide protection against disease despite the induction of antibodies that bind the pathogen of interest. In light of this, there is much interest in rationally designed subunit vaccines that direct the antibody response to protective epitopes. Here, we produced a panel of anti-idiotype antibodies able to specifically recognize the inferred germline version of the human immunodeficiency virus 1 (HIV-1) broadly neutralizing antibody b12 (iglb12). We determined the crystal structure of two anti-idiotypes in complex with iglb12 and used these anti-idiotypes to identify rare naive human B cells expressing B cell receptors with similarity to iglb12. Immunization with a multimerized version of this anti-idiotype induced the proliferation of transgenic murine B cells expressing the iglb12 heavy chain in vivo, despite the presence of deletion and anergy within this population. Together, our data indicate that anti-idiotypes are a valuable tool for the study and induction of potentially protective antibodies.
许多经过测试的疫苗尽管能诱导结合病原体的抗体，但仍不能提供针对疾病的保护。有鉴于此，人们对合理设计的亚单位疫苗产生了浓厚的兴趣，这些疫苗能将抗体反应引导到保护性表位上。在这里，我们制备了一组抗独特型抗体，能够特异性识别推断的人类免疫缺陷病毒 1（HIV-1）广谱中和抗体 b12（iglb12）的种系形式。我们确定了两种与 iglb12 复合物的抗独特型的晶体结构，并使用这些抗独特型来鉴定表达与 iglb12 相似的 B 细胞受体的罕见原始人类 B 细胞。尽管该群体中存在缺失和无能，但用这种抗独特型的多聚体版本进行免疫接种，能在体内诱导表达 iglb12 重链的转基因小鼠 B 细胞增殖。综上所述，我们的数据表明，抗独特型是研究和诱导潜在保护性抗体的有价值工具。
