Understanding the determinants of broadly neutralizing antibody (bNAb) evolution is crucial for the development of bNAb-based HIV vaccines1. Despite emerging information on cofactors that promote bNAb evolution in natural HIV-1 infections, in which the induction of bNAbs is genuinely rare2, information on the impact of the infecting virus strain on determining the breadth and specificity of the antibody responses to HIV-1 is lacking. Here we analyse the influence of viral antigens in shaping antibody responses in humans. We call the ability of a virus strain to induce similar antibody responses across different hosts its antibody-imprinting capacity, which from an evolutionary biology perspective corresponds to the viral heritability of the antibody responses. Analysis of 53 measured parameters of HIV-1-binding and neutralizing antibody responses in a cohort of 303 HIV-1 transmission pairs (individuals who harboured highly related HIV-1 strains and were putative direct transmission partners or members of an HIV-1 transmission chain) revealed that the effect of the infecting virus on the outcome of the bNAb response is moderate in magnitude but highly significant. We introduce the concept of bNAb-imprinting viruses and provide evidence for the existence of such viruses in a systematic screening of our cohort. The bNAb-imprinting capacity can be substantial, as indicated by a transmission pair with highly similar HIV-1 antibody responses and strong bNAb activity. Identification of viruses that have bNAb-imprinting capacities and their characterization may thus provide the potential to develop lead immunogens.Similarity of antibody responses in HIV-1 transmission pairs reveals a significant impact of the virus genome on imprinting antibody responses.

中文翻译：

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追踪具有广泛中和抗体反应印记的 HIV-1 毒株

了解广泛中和抗体 (bNAb) 进化的决定因素对于开发基于 bNAb 的 HIV 疫苗至关重要。尽管有关于促进自然 HIV-1 感染中 bNAb 进化的辅助因子的新信息，其中 bNAb 的诱导确实很少见 2，但有关感染病毒株对确定对 HIV-1 的抗体反应的广度和特异性的影响的信息是不足。在这里，我们分析了病毒抗原在塑造人类抗体反应中的影响。我们将病毒株在不同宿主间诱导相似抗体反应的能力称为抗体印记能力，从进化生物学的角度来看，这对应于抗体反应的病毒遗传力。分析 303 个 HIV-1 传播对（携带高度相关的 HIV-1 毒株并且是推定的直接传播伙伴或 HIV-1 传播链成员的个体）中 HIV-1 结合和中和抗体反应的 53 个测量参数) 表明感染病毒对 bNAb 反应结果的影响程度中等，但非常显着。我们引入了 bNAb 印记病毒的概念，并在对我们队列的系统筛选中提供了此类病毒存在的证据。bNAb 印记能力可能很大，正如具有高度相似的 HIV-1 抗体反应和强 bNAb 活性的传输对所表明的那样。