Department of Medicine and.
Department of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA.
J Clin Invest. 2022 Aug 1;132(15). doi: 10.1172/JCI160058.
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.
一种能够诱导中和抗体的预防性丙型肝炎病毒 (HCV) 疫苗可能是 HCV 根除的关键。然而，能够在人类中诱导抗 HCV 广泛中和抗体 (bNAbs) 的 HCV 包膜 (E1E2) 蛋白的遗传和抗原特性尚未确定。在这里，我们研究了在慢性感染或多次再感染自发清除的 HCV 感染者的纵向血浆中 bNAbs 的发展。通过测量对异种病毒组的血浆抗体中和作用，我们发现随着多种遗传上不同感染的暴露和更长时间的病毒血症，抗体反应的广度和效力增加。感染株之间更大的遗传差异与增强的中和广度无关。相反，反复暴露于抗原相关的、抗体敏感的 E1E2 与强大的 bNAb 诱导有关。这些数据表明，使用具有遗传上不同的、抗体敏感的病毒的疫苗策略是在人类中诱导强大的 bNAbs 的一种有前途的方法。
