MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow G61 1QH, UK.
Department of Gastroenterology, Queen Elizabeth University Hospital, Glasgow G51 4TF, UK.
Viruses. 2022 Jun 25;14(7):1391. doi: 10.3390/v14071391.
Hepatitis C virus (HCV) infection is a major global health problem. In the majority of cases the virus is not cleared by the host immune response and progresses to chronic infection. Studies of the neutralizing antibody responses in individuals that naturally clear infection are limited. Understanding what constitutes a successful antibody response versus one that has 'failed' and resulted in chronic infection is important to understand what type of antibody response would need to be elicited by a protective vaccine. Samples from spontaneous clearers are difficult to obtain therefore studies are often limited. In our study through HCV Research UK, we had access to a cohort of over 200 samples. We identified the samples that contained HCV neutralizing antibodies using ELISA and HCV pseudoparticle (HCVpp) assays. We then utilised mutagenesis and cross-competition analysis to determine the profile of the neutralizing antibody responses. In addition, we analysed a cohort of samples from chronic infection using the same techniques to enable direct comparison of the antibody profiles observed in both cohorts. We conclude that similar profiles are present in both cohorts indicating that it is not the neutralizing antibody response per se that determines the outcome of infection. These data will provide useful information for future HCV vaccine design.
丙型肝炎病毒(HCV)感染是一个全球性的主要健康问题。在大多数情况下,病毒不能被宿主免疫反应清除,从而进展为慢性感染。对自然清除感染的个体中中和抗体反应的研究是有限的。了解什么是成功的抗体反应,什么是“失败”并导致慢性感染,对于了解保护性疫苗需要引起什么样的抗体反应非常重要。自发清除者的样本难以获得,因此研究通常受到限制。在我们通过英国 HCV 研究中心进行的研究中,我们获得了超过 200 个样本的队列。我们使用 ELISA 和 HCV 假病毒(HCVpp)测定法来识别含有 HCV 中和抗体的样本。然后,我们利用诱变和交叉竞争分析来确定中和抗体反应的特征。此外,我们使用相同的技术分析了慢性感染的样本队列,以便能够直接比较两个队列中观察到的抗体特征。我们的结论是,两个队列中都存在相似的特征,这表明决定感染结局的不是中和抗体反应本身。这些数据将为未来的 HCV 疫苗设计提供有用的信息。