Objective 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.Met...Objective 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.Methods 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.Results 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,and0.1994 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.Conclusion 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.展开更多
Rabies is a zoonotic infectious disease with a high fatality rate.It is caused by a virus in the genus Lyssavirus and is a global public health threat.The rabies virus invades and infects cells mainly via a glycoprote...Rabies is a zoonotic infectious disease with a high fatality rate.It is caused by a virus in the genus Lyssavirus and is a global public health threat.The rabies virus invades and infects cells mainly via a glycoprotein,which may involve multiple receptors.Neutralizing antibodies against the rabies virus function by blocking the binding of the glycoprotein to a receptor or preventing the membrane fusion process.Vaccination combined with anti-rabies virus neutralizing antibodies is essential for postexposure prophylaxis for category III exposure to the rabies virus.In this review,we discussed the neutralizing epitopes of the rabies virus and the neutralization mechanism of monoclonal antibodies.The neutralizing antibodies that have been commercialized or are under development are also summarized.Our review would provide a basis for the further development of safe and effective broadspectrum neutralizing antibodies to replace the rabies virus immunoglobulin in rabies post-exposure prophylaxis.展开更多
基金supported by 2021 Beijing Key Specialty Program for Major Epidemic Prevention and Control。
文摘Objective 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.Methods 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.Results 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,and0.1994 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.Conclusion 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.
基金supported by the National Key Research and Development Program of China(No.2019YFC1200500)the National Natural Science Foundation of China(No.31902308,32170154)+1 种基金the Shandong Provincial Natural Science Foundation(No.ZR2019QC010)the Shandong Key Research and Development Program(No.2019GNC106006).
文摘Rabies is a zoonotic infectious disease with a high fatality rate.It is caused by a virus in the genus Lyssavirus and is a global public health threat.The rabies virus invades and infects cells mainly via a glycoprotein,which may involve multiple receptors.Neutralizing antibodies against the rabies virus function by blocking the binding of the glycoprotein to a receptor or preventing the membrane fusion process.Vaccination combined with anti-rabies virus neutralizing antibodies is essential for postexposure prophylaxis for category III exposure to the rabies virus.In this review,we discussed the neutralizing epitopes of the rabies virus and the neutralization mechanism of monoclonal antibodies.The neutralizing antibodies that have been commercialized or are under development are also summarized.Our review would provide a basis for the further development of safe and effective broadspectrum neutralizing antibodies to replace the rabies virus immunoglobulin in rabies post-exposure prophylaxis.
