Development and characterization of novel chimeric monoclonal antibodies for broad spectrum neutralization of rabies virus.

Autor: Kim PK; Celltrion, INC, Department of Research and Development, Incheon, Republic of Korea., Keum SJ; Celltrion, INC, Department of Research and Development, Incheon, Republic of Korea., Osinubi MOV; Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America., Franka R; Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America., Shin JY; Celltrion, INC, Department of Research and Development, Incheon, Republic of Korea., Park ST; Celltrion, INC, Department of Research and Development, Incheon, Republic of Korea., Kim MS; Celltrion, INC, Department of Research and Development, Incheon, Republic of Korea., Park MJ; Celltrion, INC, Department of Research and Development, Incheon, Republic of Korea., Lee SY; Celltrion, INC, Department of Research and Development, Incheon, Republic of Korea., Carson W; Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America., Greenberg L; Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America., Yu P; Chinese Center for Disease Control and Prevention, Beijing, China., Tao X; Chinese Center for Disease Control and Prevention, Beijing, China., Lihua W; Chinese Center for Disease Control and Prevention, Beijing, China., Tang Q; Chinese Center for Disease Control and Prevention, Beijing, China., Liang G; Chinese Center for Disease Control and Prevention, Beijing, China., Shampur M; National Institute of Mental Health and Neurosciences, Bangalore, India., Rupprecht CE; LYSSA LLC, Cummings, Georgia, United States of America., Chang SJ; Celltrion, INC, Department of Research and Development, Incheon, Republic of Korea.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2017 Oct 18; Vol. 12 (10), pp. e0186380. Date of Electronic Publication: 2017 Oct 18 (Print Publication: 2017).
DOI: 10.1371/journal.pone.0186380
Abstrakt: Current post-exposure prophylaxis for rabies virus infection has several limitations in terms of supply, cost, safety, and efficacy. Attempts to replace human or equine rabies immune globulins (HRIG or ERIG) have been made by several companies and institutes. We developed potent monoclonal antibodies to neutralize a broad spectrum of rabies viruses by screening hybridomas received from the U.S. Centers for Disease Control and Prevention (CDC). Two kinds of chimeric human antibodies (chimeric #7 and #17) were constructed by cloning the variable regions from selected hybridomas and the constant region of a human antibody. Two antibodies were bound to antigenic site III and I/IV, respectively, and were able to neutralize 51 field isolates of rabies virus that were isolated at different times and places such as Asia, Africa, North America, South America, and Australia. These two antibodies neutralize rabies viruses with high efficacy in an in vivo test using Syrian hamster and mouse models and show low risk for adverse immunogenicity.
Databáze: MEDLINE