[Progress and prospect of clinical application of anti-rabies virus monoclonal antibody preparation].
作者: X J Lyu ; G M Dong ; X Q Liu ; S Liu ; C Liu ; Q J Chen ; W W Yin ; C L Wang
Rabies is a severe infectious disease caused by the rabies virus, which seriously damages the central nervous system. Once it occurs, the fatality rate is close to 100%. The World Health Organization's position paper on rabies vaccines recognizes that rabies immunoglobulin (RIG) should be used for post-exposure prophylaxis (PEP) in all category Ⅲ exposures for the first time, as well as in category II exposures that suffer from severe immune deficiency, long-term massive use of immunosuppressants, and head and face exposure. The anti-rabies virus monoclonal antibody has high purity and specific activity, can be produced on a sustainable scale, and has no risk of blood source virus contamination. Preclinical pharmacodynamic studies and clinical trial results of the anti-rabies virus monoclonal antibody combination preparation have confirmed that the preparation has a broad-spectrum neutralization effect on the rabies virus. Additionally, its combined application with the vaccine has little impact on the active immunity of the vaccine, and the conversion of serum circulating antibodies to the protective level is fast and lasts for a long time. Therefore, the anti-rabies virus monoclonal antibody combination preparation shows great potential for clinical application in PEP.
2022-09-20·Biomedical and environmental sciences : BES
Rabies Virus Neutralizing Activity, Safety, and Immunogenicity of Recombinant Human Rabies Antibody Compared with Human Rabies Immunoglobulin in Healthy Adults.
作者: Jun Nan Zhang ; Ya Juan Meng ; Yun Hua Bai ; Yu Feng Li ; Li Qing Yang ; Nian Min Shi ; Hui Xia Han ; Jian Gao ; Li Juan Zhu ; Shu Ping Li ; Jing Zhang ; Qin Hua Zhao ; Xiu Qin Wang ; Jing Shuang Wei ; Le Min Ren ; Chen Hua Cao ; Chen Chen ; Wei Zhao ; Li Li
Preliminary assessment of rabies virus neutralizing activity, safety and immunogenicity of a recombinant human rabies antibody (NM57) compared with human rabies immunoglobulin (HRIG) in Chinese healthy adults.
Subjects were randomly (1:1:1) allocated to Groups A (20 IU/kg NM57), B (40 IU/kg NM57), or C (20 IU/kg HRIG). One injection was given on the day of enrollment. Blood samples were collected on days -7 to 0 (pre-injection), 3, 7, 14, 28, and 42. Adverse events (AEs) and serious AEs (SAEs) were recorded over a period of 42 days after injection.
All 60 subjects developed detectable rabies virus neutralizing antibodies (RVNAs) (> 0.05 IU/mL) on days 3, 7, 14, 28, and 42. The RVNA levels peaked on day 3 in all three groups, with a geometric mean concentration (GMC) of 0.2139 IU/mL in Group A, 0.3660 IU/mL in Group B, and 0.1994 IU/mL in Group C. At each follow-up point, the GMC in Group B was significantly higher than that in Groups A and C. The areas under the antibody concentration curve over 0-14 days and 0-42 days in Group B were significantly larger than those in Groups A and C. Fifteen AEs were reported. Except for one grade 2 myalgia in Group C, the other 14 were all grade 1. No SAEs were observed.
The rabies virus neutralizing activity of 40 IU/kg NM57 was superior to that of 20 IU/kg NM57 and 20 IU/kg HRIG, and the rabies virus neutralizing activity of 20 IU/kg NM57 and 20 IU/kg HRIG were similar. Safety was comparable between NM57 and HRIG.
2022-01-25·Travel medicine and infectious disease2区 · 医学
Efficacy of ormutivimab, a novel recombinant human anti-rabies monoclonal antibody, in post-exposure prophylaxis animal models.
2区 · 医学
作者: Li-Li Zhai ; Hui Wang ; Wei Zhao ; Shou-Feng Zhang ; Fa-Ming Miao ; Yang Cao ; Chen Chen ; Yu-Feng Li ; Jie Gao ; Ruo-Yun Lv ; Shi-Xiong Zhang ; Jia-Bin Cao ; Xu-Fan Zhang ; Ming-Ming Yang ; Bin Zhang ; Jing Zhao ; Jing-Shuang Wei ; Jian Gao
Human rabies is a serious public health problem that can't be ignored. Rabies immune globulin (RIG) is an indispensable component of rabies post-exposure prophylaxis (PEP). However, current PEP relies on RIG purified from pooled human or equine plasma, which are either in chronic shortage or associated with safety concerns. Monoclonal antibodies have become widely accepted as safer and more cost-effective alternatives to RIG products in recent years. Here, we assessed the neutralization breadth of human monoclonal antibody ormutivimab and its protective efficacy in PEP models. Ormutivimab was able to neutralize a broad panel of Chinese prevalent street RABVs with neutralizing potency form 198-1487.6 IU/mL. Furthermore, ormutivimab offered comparable protection to that with HRIG both at standard doses (20 IU/kg) and higher doses (100 IU/kg and 200 IU/kg). The interference of ormutivimab on vaccine potency was also analyzed and found slightly reduced neutralizing antibody titers similar to HRIG. The broad-spectrum neutralization activities, highly protective potency, and rapid onset of action make ormutivimab an effective candidate for human rabies PEP.