B cell engagement with HIV-1 founder virus envelope predicts development of broadly neutralizing antibodies.

Determining which immunological mechanisms contribute to the development of broad neutralizing antibodies (bNAbs) during HIV-1 infection is a major goal to inform vaccine design. Using samples from a longitudinal HIV-1 acute infection cohort, we found key B cell determinants within the first 14–43 days of viremia predict the development of bNAbs years later. Individuals who develop neutralization breadth had significantly higher B cell engagement with the autologous founder HIV Envelope (Env) within 1 month of initial viremia. A higher frequency of founder Env-specific naïve B cells was associated with increased B cell activation and differentiation, and predictive of bNAb development. These data demonstrate that the initial B cell interaction with the founder HIV Env is important for the development of broadly neutralizing antibodies, and provide evidence that events within HIV acute infection lead to downstream functional outcomes. Interrogating how HIV-infected patients develop broadly neutralizing antibodies can inform vaccine design. Townsley et al. show that elevated B cell interactions with the HIV founder envelope glycoprotein within the first month of infection lead to increased B cell activation and differentiation, which predict development of neutralization breadth years later.

确定在HIV - 1感染期间哪些免疫机制有助于广谱中和抗体（bNAbs）的产生是为疫苗设计提供依据的一个主要目标。利用来自一个HIV - 1急性感染纵向队列的样本，我们发现在病毒血症出现后的前14 - 43天内的关键B细胞决定因素可预测数年后bNAbs的产生。产生中和广度的个体在初次病毒血症的1个月内，其B细胞与自体始祖HIV包膜蛋白（Env）的结合显著更高。始祖Env特异性初始B细胞频率越高，与B细胞活化和分化的增加相关，并可预测bNAb的产生。这些数据表明，初始B细胞与始祖HIV Env的相互作用对于广谱中和抗体的产生很重要，并提供证据表明HIV急性感染期间的事件会导致下游的功能性结果。 探究HIV感染患者如何产生广谱中和抗体可为疫苗设计提供信息。汤斯利等人表明，在感染的第一个月内B细胞与HIV始祖包膜糖蛋白的相互作用增强会导致B细胞活化和分化增加，这可预测数年后中和广度的产生。