Laboratory of Virology, National Institute for Infectious Diseases "Lazzaro Spallanzani" (IRCCS), 00149 Rome, Italy.
Department of Biology and Biotechnology "Charles Darwin", Sapienza University of Rome, 00100 Rome, Italy.
Viruses. 2024 Aug 21;16(8):1337. doi: 10.3390/v16081337.
Therapy against the Hepatitis C virus (HCV) has significantly improved with the introduction of direct-acting antiviral drugs (DAAs), achieving over 95% sustained virological response (SVR). Despite this, the development of an effective anti-HCV vaccine remains a critical challenge due to the low number of patients treated with DAAs and the occurrence of HCV reinfections in high-risk groups. Current vaccine strategies aim to stimulate either B-cell or T-cell responses. Vaccines based on E1 and E2 proteins can elicit broad cross-neutralizing antibodies against all major HCV genotypes, though with varying efficiencies and without full protection against infection. In humans, the neutralizing antibodies induced by such vaccines mainly target the AR3 region, but their levels are generally insufficient for broad neutralization. Various HCV proteins expressed through different viral vectors have been utilized to elicit T cell immune responses, showing sustained expansion of HCV-specific effector memory T cells and improved proliferation and polyfunctionality of memory T cells over time. However, despite these advancements, the frequency and effectiveness of T-cell responses remain limited.
针对丙型肝炎病毒 (HCV) 的治疗方法随着直接作用抗病毒药物 (DAA) 的引入而显著改善，实现了超过 95%的持续病毒学应答 (SVR)。尽管如此，由于接受 DAA 治疗的患者数量较少以及高危人群中 HCV 再感染的发生，开发有效的抗 HCV 疫苗仍然是一个重大挑战。目前的疫苗策略旨在刺激 B 细胞或 T 细胞反应。基于 E1 和 E2 蛋白的疫苗可以诱导针对所有主要 HCV 基因型的广泛中和抗体，但效率各不相同，并且不能完全预防感染。在人类中，此类疫苗诱导的中和抗体主要针对 AR3 区域，但它们的水平通常不足以进行广泛中和。已经利用通过不同病毒载体表达的各种 HCV 蛋白来引发 T 细胞免疫反应，显示出 HCV 特异性效应记忆 T 细胞的持续扩增，并且随着时间的推移，记忆 T 细胞的增殖和多功能性得到改善。然而，尽管取得了这些进展，T 细胞反应的频率和有效性仍然有限。
