Advancing ORFV-Based Therapeutics to the Clinical Stage.

IF 9 2区 医学 Q1 VIROLOGY
Matthias Helmold, Ralf Amann
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引用次数: 0

Abstract

The Orf virus (ORFV) is the prototype member of the parapoxvirus family and has long been recognized for its robust immunogenicity, favourable safety profile and its ability to stimulate both cellular and humoural immune responses without inducing significant anti-vector immunity. Despite these inherent advantages, early applications of ORFV-based technologies were limited by challenges in manufacturing scalability and uncertainties regarding clinical safety in humans. However, recent breakthroughs have transformed this therapeutic landscape. A landmark achievement is the development of Prime-2-CoV, an ORFV-based anti-COVID-19 vaccine that has advanced into human clinical trials, providing the first clinical evidence of live ORFV's feasibility, safety and immunogenicity. This milestone, together with the establishment of a good manufacturing practice (GMP)-compliant production process and comprehensive preclinical evaluations, has laid a robust foundation for broader clinical applications of ORFV-based therapeutics. Moreover, the use of ORFV as an oncolytic virus therapy has shown promising results, effectively converting immunologically 'cold' tumours into 'hot' ones, underscoring its versatility as a therapeutic platform. In this review, we critically assess recent advances in ORFV-based therapeutics, with a particular focus on vaccine development and oncolytic virotherapy (OVT). We thoroughly discuss the milestones and impact of the first ORFV-based clinical trial, outline strategies for optimizing the technology and provide insights into overcoming remaining challenges. Collectively, these advancements position ORFV as a highly promising and versatile platform for next-generation prophylactic and therapeutic interventions in both human and veterinary medicine, while also providing a roadmap for future innovations.

将基于orfv的疗法推进到临床阶段。
口蹄疫病毒(ORFV)是副痘病毒家族的原型成员,长期以来因其强大的免疫原性、良好的安全性以及刺激细胞和体液免疫反应而不诱导显著的抗媒介免疫的能力而得到认可。尽管有这些固有的优势,但基于orfv技术的早期应用受到制造可扩展性挑战和人体临床安全性不确定性的限制。然而,最近的突破已经改变了这一治疗领域。一项里程碑式的成就是基于ORFV的抗covid -19疫苗Prime-2-CoV的开发,该疫苗已进入人体临床试验,首次提供了活体ORFV可行性、安全性和免疫原性的临床证据。这一里程碑,连同良好生产规范(GMP)生产流程的建立和全面的临床前评估,为orfv疗法更广泛的临床应用奠定了坚实的基础。此外,使用ORFV作为溶瘤病毒治疗已经显示出有希望的结果,有效地将免疫上的“冷”肿瘤转化为“热”肿瘤,强调了其作为治疗平台的多功能性。在这篇综述中,我们批判性地评估了基于orfv的治疗方法的最新进展,特别关注疫苗开发和溶瘤病毒治疗(OVT)。我们深入讨论了第一个基于orfv的临床试验的里程碑和影响,概述了优化技术的策略,并提供了克服剩余挑战的见解。总的来说,这些进步使ORFV成为人类和兽医学下一代预防和治疗干预的一个非常有前途的多功能平台,同时也为未来的创新提供了路线图。
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来源期刊
Reviews in Medical Virology
Reviews in Medical Virology 医学-病毒学
CiteScore
21.40
自引率
0.90%
发文量
88
期刊介绍: Reviews in Medical Virology aims to provide articles reviewing conceptual or technological advances in diverse areas of virology. The journal covers topics such as molecular biology, cell biology, replication, pathogenesis, immunology, immunization, epidemiology, diagnosis, treatment of viruses of medical importance, and COVID-19 research. The journal has an Impact Factor of 6.989 for the year 2020. The readership of the journal includes clinicians, virologists, medical microbiologists, molecular biologists, infectious disease specialists, and immunologists. Reviews in Medical Virology is indexed and abstracted in databases such as CABI, Abstracts in Anthropology, ProQuest, Embase, MEDLINE/PubMed, ProQuest Central K-494, SCOPUS, and Web of Science et,al.
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