Development of a Highly Protective Combination Monoclonal Antibody Therapy against Chikungunya Virus

• DOI: 10.1371/journal.ppat.1003312
• Publication Date: 2013-04-18T21:03:28Z
• Authors: Pankaj Pal; Kimberly A. Dowd; James D. Brien; Melissa A. Edeling; Sergey Gorlatov; Syd Johnson; Iris Lee; Wataru Akahata; Gary J. Nabel; Mareike K. S. Ric...; Jolanda M. Smit; Daved H. Fremont; Theodore C. Pierson; Mark T. Heise; Michael S. Diamond
• Keywords: 0301 basic medicine; QH301-705.5; SEMLIKI-FOREST-VIRUS; 610; Receptor, Interferon alpha-beta; WEST-NILE-VIRUS; Antibodies, Viral; Cell Line; Mice; 03 medical and health sciences; FUSION; E2 GLYCOPROTEIN; Viral Envelope Proteins; Aedes; INFECTION; Chlorocebus aethiops; Animals; Biology (General); Vero Cells; Mice, Knockout; Viral Structural Proteins; Alphavirus Infections; ANTIGENIC SITE; Antibodies, Monoclonal; MOUSE MODEL; 3T3 Cells; RC581-607; Antibodies, Neutralizing; 3. Good health; Mice, Inbred C57BL; MICE; Chikungunya Fever; ESCAPE MUTANTS; Immunologic diseases. Allergy; Chikungunya virus; SINDBIS VIRUS; Research Article

Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes global epidemics of debilitating polyarthritis in humans. As there pressing need for the development therapeutic agents, we screened 230 new mouse anti-CHIKV monoclonal antibodies (MAbs) their ability to inhibit infection all three CHIKV genotypes. Four 36 neutralizing MAbs (CHK-102, CHK-152, CHK-166, and CHK-263) provided complete protection against lethality as prophylaxis highly susceptible immunocompromised mice lacking type I IFN receptor (Ifnar(-/-) ) mapped distinct epitopes on E1 E2 structural proteins. most protective MAb, was humanized, shown block viral fusion, require Fc effector function optimal activity vivo. In post-exposure trials, administration single dose combination two (CHK-102+CHK-152 or CHK-166+CHK-152) limited resistance protected disease when given 24 hours before CHIKV-induced death. Selected pairs may be promising treatment option