Generation and characterization of a human neutralizing bivalent antibody Fab094-DDD against rabies virus
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    Abstract:

    Objective:We sought to produce a human specific anti-rabies-virus bivalent antibody with neutralizing activity by using the dimer effect of RII’s dimerization and docking domain(DDD)in protein kinase A(PKA). Methods:Linker-C-DDD sequence was optimized and synthesized. Fd section and light chain variable region (Vκ) of anti-rabies virus Fab094 were amplified. Fd section of Fab094 and linker-C-DDD gene were recombined using overlap PCR. Fd-DDD and Vκ were cloned into eukaryotic expression vectors and both vectors were transfected into 293 free style cells. Fab094-DDD antibody was expressed and purified. The immunological features of Fab094-DDD was detected by SDS-PAGE,Western blot assay,enzyme-linked immunosorbent assay(ELISA),co-IP,affinity test and indirect immunofluorescence test. The neutralizing activity of Fab094-DDD was detected by fluorescent antibody virus neutralization test. Results:The results demonstrated that the eukaryotic expression vectors of the human specific anti-rabies virus bivalent Fab094-DDD antibody were successfully constructed. The antibody effectively recognized the antigen and specifically combined the rabies virus,and the neutralization titer of the antibody was 213.2 U/mg. Conclusion:We successfully generated a bivalent Fab094-DDD antibody against rabies virus,and the antibody showed high neutralizing activity. Fab094-DDD antibody could establish the foundation for the treatment of rabies and could be applied to the construction of other bispecific human specific antibodies.

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耿以如,熊四平,唐 奇,张 晓,陈 雅,徐亚如,周 荧,仇镇宁,冯振卿,朱 进.人源特异性抗狂犬病毒二价Fab094-DDD抗体的制备及鉴定[J].南京医科大学学报(自然科学版英文版),2016,(6):693-699.

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  • Received:February 16,2016
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  • Online: June 15,2016
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