Hrabal Isabella, Aliabadi Elmira, Reiche Sven, Weber Saskia, Holicki Cora M, Schmid Laura, Fast Christine, Schröder Charlotte, Gutjahr Benjamin, Behrendt Patrick, Groschup Martin H, Eiden Martin
Institute for Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut, Greifswald - Insel Riems, Germany.
Institute for Experimental Virology, Centre for Experimental and Clinical Infection Research, TWINCORE, Hannover, Germany.
Sci Rep. 2025 Mar 28;15(1):10795. doi: 10.1038/s41598-025-95992-x.
Hepatitis E virus (HEV) poses a significant risk to human health. In Europe, the majority of HEV infection are caused by the zoonotic genotype 3 (HEV-3), which can cause chronic hepatitis E in immunocompromised patients and those with pre-existing liver disease, and may eventually develop into fatal liver cirrhosis. In this study, we examined the effectiveness of a monoclonal antibody (MAb) treatment strategy using a well established HEV-3 pig model with intravenous infection. For this purpose, nine MAbs raised against the viral capsid protein were generated and the neutralizing activities were compared using in vitro assays. The antibody with the highest neutralizing activity, MAb 5F6A1, was selected for an in vivo study in pigs infected with HEV-3. Following the initial infection of pigs with HEV-3, MAb 5F6A1 was administered intravenously one and seven days post-infection. The results suggest MAb 5F6A1 significantly reduced viremia and virus shedding in pigs infected with HEV-3. This study provides significant insight into the dynamics of HEV infection in pigs and highlights the efficacy of MAb based therapy as an option for treating HEV in porcine hosts and, potentially, humans.
戊型肝炎病毒（HEV）对人类健康构成重大风险。在欧洲，大多数戊型肝炎感染是由人畜共患的3型基因型（HEV-3）引起的，这种病毒可导致免疫功能低下患者和已有肝病患者发生慢性戊型肝炎，并可能最终发展为致命的肝硬化。在本研究中，我们使用已建立的静脉感染HEV-3猪模型，检验了单克隆抗体（MAb）治疗策略的有效性。为此，制备了9种针对病毒衣壳蛋白的单克隆抗体，并通过体外试验比较了它们的中和活性。选择中和活性最高的抗体MAb 5F6A1，对感染HEV-3的猪进行体内研究。在用HEV-3初次感染猪后，在感染后第1天和第7天静脉注射MAb 5F6A1。结果表明，MAb 5F6A1显著降低了感染HEV-3猪的病毒血症和病毒排泄。本研究为猪戊型肝炎感染的动态变化提供了重要见解，并突出了基于单克隆抗体的疗法作为治疗猪宿主乃至人类戊型肝炎的一种选择的有效性。
