The World Health Organization, Geneva, Switzerland; School of Public Health and Community Medicine, UNSW Sydney, NSW, Australia.
School of Public Health and Community Medicine, UNSW Sydney, NSW, Australia; Clinical and Population Perinatal Health Research, The University of Sydney Northern Clinical School, NSW, Australia.
Vaccine. 2019 Oct 3;37 Suppl 1:A132-A139. doi: 10.1016/j.vaccine.2018.11.004. Epub 2018 Nov 29.
Despite successful control in many parts of the world, rabies virus continues to result in tens of thousands of deaths each year. Death from rabies can be prevented by timely and appropriate post exposure prophylaxis including wound cleaning and administration of vaccine and rabies immunoglobulin. Currently, rabies immunoglobulin is derived from the blood plasma of horses or humans and has several limitations relating to supply, cost and quality. Monoclonal antibodies produced through recombinant DNA technologies could potentially overcome these limitations. The first anti-rabies monoclonal antibody has recently gained regulatory approval in India and there are several other candidates being evaluated in clinical trials. Given the advances in the field, rabies monoclonal antibodies have been recently considered by the World Health Organization's Strategic Advisory Group of Experts on Immunization and included in updated WHO immunization policy recommendations for rabies published in April 2018. This article reviews the current landscape of the clinical trial development of anti-rabies monoclonal antibodies and the historical clinical trial pathways followed for blood-derived rabies immunoglobulin before discussing challenges in the clinical evaluation, regulatory approval, uptake and monitoring of these products.
尽管在世界许多地区已成功控制,但狂犬病病毒每年仍导致数万人死亡。通过及时和适当的接触后预防措施,包括伤口清洗和疫苗以及狂犬病免疫球蛋白的使用,可以预防狂犬病导致的死亡。目前,狂犬病免疫球蛋白来源于马或人的血浆,存在与供应、成本和质量相关的一些限制。通过重组 DNA 技术生产的单克隆抗体可能会克服这些限制。最近,第一种抗狂犬病单克隆抗体已在印度获得监管批准,还有其他几种候选药物正在临床试验中进行评估。鉴于该领域的进展,世界卫生组织免疫战略咨询专家组最近考虑将狂犬病单克隆抗体纳入 2018 年 4 月发布的更新后的世卫组织狂犬病免疫政策建议。本文回顾了抗狂犬病单克隆抗体临床试验开发的现状,以及血液来源狂犬病免疫球蛋白的历史临床试验途径,然后讨论了这些产品在临床评估、监管批准、采用和监测方面的挑战。