Activating precursor B cell receptors of HIV-1 broadly neutralizing antibodies requires specifically designed immunogens. Here, we compared the abilities of three such germline-targeting immunogens against the VRC01-class receptors to activate the targeted B cells in transgenic mice expressing the germline VH of the VRC01 antibody but diverse mouse light chains. Immunogen-specific VRC01-like B cells were isolated at different time points after immunization, their VH and VL genes were sequenced, and the corresponding antibodies characterized. VRC01 B cell sub-populations with distinct cross-reactivity properties were activated by each immunogen, and these differences correlated with distinct biophysical and biochemical features of the germline-targeting immunogens. Our study indicates that the design of effective immunogens to activate B cell receptors leading to protective HIV-1 antibodies will require a better understanding of how the biophysical properties of the epitope and its surrounding surface on the germline-targeting immunogen influence its interaction with the available receptor variants in vivo.

激活 HIV-1 广泛中和抗体的前体 B 细胞受体需要专门设计的免疫原。在这里，我们比较了三种此类针对 VRC01 类受体的种系靶向免疫原在表达 VRC01 抗体的种系 VH 但小鼠轻链不同的转基因小鼠中激活靶向 B 细胞的能力。免疫原特异性 VRC01 样 B 细胞在免疫接种后的不同时间点分离，对它们的 VH 和 VL 基因进行测序，并表征相应的抗体。具有不同交叉反应特性的 VRC01 B 细胞亚群被每种免疫原激活，这些差异与生殖系靶向免疫原的不同生物物理和生化特征相关。体内。