Bakacs Tibor, Sandig Volker, Kovesdi Imre
Department of Probability, Alfred Renyi Institute of Mathematics, The Eotvos Lorand Research Network (ELKH), 1053 Budapest, Hungary.
ProBioGen AG, 13086 Berlin, Germany.
Pharmaceuticals (Basel). 2023 Feb 1;16(2):226. doi: 10.3390/ph16020226.
Practically the entire global population is infected by herpesviruses that establish lifelong latency and can be reactivated. Alpha-herpesviruses, herpes simplex viruses 1 and 2 (HSV-1/HSV-2) and varicella zoster virus (VZV), establish latency in sensory neurons and then reactivate to infect epithelial cells in the mucosa or skin, resulting in a vesicular rash. Licensed antivirals inhibit virus replication, but do not affect latency. On reactivation, VZV causes herpes zoster, also known as shingles. The 76-year-old first author of this paper published an autobiography of his own severe herpes zoster ophthalmicus (HZO) infection with orbital edema, which is considered an emergency condition. Acyclovir (ACV) treatment was complemented with an immunostimulatory viral therapy, which resolved most symptoms within a few days. The orally administered live-attenuated infectious bursal disease vaccine virus (IBDV) delivers its double-stranded RNA (dsRNA) cargo to host cells and activates the natural antiviral interferon (IFN) gene defense system from within the host cells. IBDV has already been demonstrated to be safe and effective against five different families of viruses, hepatitis A virus (HAV), hepatitis B and C virus (HBV/HCV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and varicella zoster virus (VZV). Here we propose a short phase I/II trial in elderly shingles patients who will be assigned to receive either ACV monotherapy or ACV combined with R903/78, an attenuated immunostimulatory IBDV strain. The primary endpoints will be safety, but the efficacy of the combination therapy against the ACV monotherapy also will be assessed.
实际上，几乎全球所有人都感染过疱疹病毒，这些病毒会建立终身潜伏感染并可能重新激活。甲型疱疹病毒，即单纯疱疹病毒1型和2型（HSV-1/HSV-2）以及水痘带状疱疹病毒（VZV），在感觉神经元中建立潜伏感染，然后重新激活以感染黏膜或皮肤中的上皮细胞，导致水疱性皮疹。已获批的抗病毒药物可抑制病毒复制，但不影响潜伏感染。VZV重新激活时会引发带状疱疹，也称为缠腰龙。本文76岁的第一作者发表了一篇关于他自己严重眼部带状疱疹（HZO）感染并伴有眼眶水肿的自传，这被视为一种紧急情况。阿昔洛韦（ACV）治疗辅以免疫刺激病毒疗法，在几天内缓解了大多数症状。口服的减毒传染性法氏囊病疫苗病毒（IBDV）将其双链RNA（dsRNA）运送到宿主细胞内，并从宿主细胞内部激活天然抗病毒干扰素（IFN）基因防御系统。IBDV已被证明对五种不同病毒家族安全有效，即甲型肝炎病毒（HAV）、乙型和丙型肝炎病毒（HBV/HCV）、严重急性呼吸综合征冠状病毒2（SARS-CoV-2）以及水痘带状疱疹病毒（VZV）。在此，我们提议对老年带状疱疹患者进行一项短期的I/II期试验，这些患者将被分配接受ACV单药治疗或ACV联合R903/78治疗，R903/78是一种减毒的免疫刺激IBDV毒株。主要终点将是安全性，但也将评估联合疗法相对于ACV单药治疗的疗效。
