KEM Hospital and Seth GS Medical College, Mumbai, India.
Vaccine. 2012 Nov 26;30(50):7315-20. doi: 10.1016/j.vaccine.2012.09.027. Epub 2012 Sep 23.
Rabies is an essentially fatal disease that is preventable with the timely administration of post-exposure prophylaxis (PEP). The high cost of PEP, which includes vaccine and hyperimmune globulin, is an impediment to the goal of preventing rabies in the developing world. Recently a recombinant human IgG(1) anti-rabies monoclonal antibody (SII RMab) has been developed in India to replace serum-derived rabies immunoglobulin. The present study was conducted to demonstrate the safety of SII RMab and to determine the dose resulting in neutralizing serum antibody titers comparable to human rabies immunoglobulin (HRIG) when administered in conjunction with rabies vaccine in a simulated PEP regimen.
This randomized, open label, dose-escalation phase 1 study was conducted in healthy adults at a large tertiary care, referral, public hospital in India. Safety was assessed by active surveillance for adverse events along with standard laboratory evaluations and measurement of anti-drug antibodies (ADA). Anti-rabies antibody levels were measured by rapid fluorescent focus inhibition test (RFFIT) and ELISA. The study duration was 365 days.
SII RMab was well tolerated with similar frequency of local injection site reactions to HRIG. The geometric mean concentrations of rabies neutralizing antibody in the vaccine plus SII RMab 10 IU/kg cohort were comparable to the vaccine plus HRIG 20 IU/kg cohort throughout the 365-day study period; day 14 geometric mean concentrations 23.4 IU/ml (95% CI 14.3, 38.2) vs. 15.3 IU/ml (95% CI 7.72, 30.3; p=NS), respectively. Future post-exposure prophylaxis studies of SII RMab at a dose of 10 IU/kg in conjunction with vaccine are planned.
狂犬病是一种基本上致命的疾病，可以通过及时进行暴露后预防（PEP）来预防。PEP 的高成本，包括疫苗和狂犬病免疫球蛋白，是发展中国家预防狂犬病目标的一个障碍。最近，印度开发了一种重组人 IgG(1)抗狂犬病单克隆抗体（SII RMab），以替代血清源性狂犬病免疫球蛋白。本研究旨在证明 SII RMab 的安全性，并确定在模拟 PEP 方案中与狂犬病疫苗联合使用时，产生与狂犬病免疫球蛋白（HRIG）相当的中和血清抗体滴度的剂量。
这项随机、开放标签、剂量递增的 1 期研究在印度一家大型三级保健、转诊、公立医院的健康成年人中进行。通过主动监测不良反应以及标准实验室评估和抗药物抗体（ADA）测量来评估安全性。狂犬病抗体水平通过快速荧光灶抑制试验（RFFIT）和 ELISA 测量。研究持续 365 天。
SII RMab 耐受性良好，与 HRIG 相比，局部注射部位反应的频率相似。疫苗加 SII RMab 10 IU/kg 组的狂犬病中和抗体几何平均浓度在整个 365 天研究期间与疫苗加 HRIG 20 IU/kg 组相当；第 14 天的几何平均浓度分别为 23.4 IU/ml（95%CI 14.3，38.2）和 15.3 IU/ml（95%CI 7.72，30.3；p=NS）。计划在未来的 SII RMab 研究中，在疫苗的基础上加用 10 IU/kg 的剂量进行 PEP。
