A prophylactic hepatitis C virus (HCV) vaccine that elicits neutralizing antibodies could be key to HCV eradication. However, the genetic and antigenic properties of HCV envelope (E1E2) proteins capable of inducing anti-HCV broadly neutralizing antibodies (bNAbs) in humans have not been defined. Here, we investigated the development of bNAbs in longitudinal plasma of HCV-infected persons with persistent infection or spontaneous clearance of multiple reinfections. By measuring plasma antibody neutralization of a heterologous virus panel, we found that the breadth and potency of the antibody response increased upon exposure to multiple genetically distinct infections and with longer duration of viremia. Greater genetic divergence between infecting strains was not associated with enhanced neutralizing breadth. Rather, repeated exposure to antigenically related, antibody-sensitive E1E2s was associated with potent bNAb induction. These data reveal that a prime-boost vaccine strategy with genetically distinct, antibody-sensitive viruses is a promising approach to inducing potent bNAbs in humans.

中文翻译：

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反复接触异源丙型肝炎病毒与中和抗体广度和效力增强相关


能够引发中和抗体的预防性丙型肝炎病毒（HCV）疫苗可能是根除丙型肝炎病毒的关键。然而，能够在人类体内诱导抗 HCV 广泛中和抗体 (bNAb) 的 HCV 包膜 (E1E2) 蛋白的遗传和抗原特性尚未确定。在这里，我们研究了持续感染或多次再感染自发清除的 HCV 感染者纵向血浆中 bNAb 的发展。通过测量异源病毒组的血浆抗体中和作用，我们发现，在暴露于多种遗传上不同的感染以及病毒血症持续时间较长的情况下，抗体反应的广度和效力增加。感染菌株之间更大的遗传差异与中和广度的增强无关。相反，反复暴露于抗原相关、抗体敏感的 E1E2 与有效的 bNAb 诱导相关。这些数据表明，使用基因独特、抗体敏感的病毒进行初免-加强疫苗策略是在人类中诱导有效 bNAb 的一种有前途的方法。