Department of Immunology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom.
Department of Virology, Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom.
Front Immunol. 2023 Mar 3;14:1135834. doi: 10.3389/fimmu.2023.1135834. eCollection 2023.
The global polio eradication campaign has had remarkable success in reducing wild-type poliovirus infection, largely built upon the live attenuated Sabin oral poliovirus vaccine. Whilst rare, vaccine poliovirus strains may cause infection and subsequently revert to a neurovirulent type, termed vaccine-derived poliovirus (VDPV). Persistent, vaccine derived infection may occur in an immunocompromised host (iVDPV), where it is a recognised complication following receipt of the Sabin vaccine. This has significant implications for the global polio eradication campaign and there is currently no agreed global strategy to manage such patients.Here we describe a case of a 50-year-old man with common variable immune deficiency, persistently infected with a neurovirulent vaccine-derived type 2 poliovirus following vaccination in childhood. iVDPV infection had proven resistant to multiple prior attempts at treatment with human breast milk, ribavirin and oral administration of a normal human pooled immunoglobulin product. His iVDPV infection subsequently resolved after 12 days treatment with remdesivir, an adenosine analogue prodrug that is an inhibitor of viral RNA-dependent RNA polymerase, administered as treatment for a prolonged, moderate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. iVDPV from the patient, isolated prior to treatment, was subsequently demonstrated to be sensitive to remdesivir in vitro. Based on the observations made in this case, and the mechanistic rationale for use with iVDPV, there is strong justification for further clinical studies of remdesivir treatment as a potentially curative intervention in patients with iVDPV infection.
全球根除脊髓灰质炎运动在减少野生型脊灰病毒感染方面取得了显著成功,这主要得益于口服脊髓灰质炎减毒活疫苗(Sabin 疫苗)。虽然罕见,但疫苗衍生的脊灰病毒株可能会引起感染,并随后恢复为神经毒力类型,称为疫苗衍生脊灰病毒(VDPV)。在免疫功能低下的宿主(iVDPV)中,疫苗衍生的持续性感染可能会发生,这是在接种 Sabin 疫苗后公认的并发症。这对全球根除脊髓灰质炎运动具有重大影响,目前尚无针对此类患者的全球公认管理策略。在这里,我们描述了一名 50 岁男性的病例,他患有普通可变免疫缺陷,在儿童时期接种疫苗后持续感染神经毒力疫苗衍生 2 型脊灰病毒。iVDPV 感染已被证明对先前使用人乳、利巴韦林和口服正常人混合免疫球蛋白产品治疗的多次尝试具有耐药性。在使用瑞德西韦治疗 12 天后,他的 iVDPV 感染随后得到解决,瑞德西韦是一种腺苷类似物前药,是病毒 RNA 依赖性 RNA 聚合酶的抑制剂,用于治疗持续时间较长的中度严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)感染。在治疗前从患者中分离出的 iVDPV 随后在体外被证明对瑞德西韦敏感。基于该病例的观察结果以及使用 iVDPV 的机制原理,有充分理由进一步开展瑞德西韦治疗的临床研究,作为 iVDPV 感染患者的潜在治愈性干预措施。