Journal article
Development of a Highly Protective Combination Monoclonal Antibody Therapy against Chikungunya Virus
P Pal, KA Dowd, JD Brien, MA Edeling, S Gorlatov, S Johnson, I Lee, W Akahata, GJ Nabel, MKS Richter, JM Smit, DH Fremont, TC Pierson, MT Heise, MS Diamond
Plos Pathogens | PUBLIC LIBRARY SCIENCE | Published : 2013
Abstract
Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes global epidemics of a debilitating polyarthritis in humans. As there is a pressing need for the development of therapeutic agents, we screened 230 new mouse anti-CHIKV monoclonal antibodies (MAbs) for their ability to inhibit infection of all three CHIKV genotypes. Four of 36 neutralizing MAbs (CHK-102, CHK-152, CHK-166, and CHK-263) provided complete protection against lethality as prophylaxis in highly susceptible immunocompromised mice lacking the type I IFN receptor (Ifnar-/-) and mapped to distinct epitopes on the E1 and E2 structural proteins. CHK-152, the most protective MAb, was humanized, shown to block viral..
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Awarded by National Institute of Allergy and Infectious Diseases
Funding Acknowledgements
U54 AI 057157: Southeast Regional Center of Excellence for Emerging Infections and Biodefense (to MTH), NIH grant R01-AI104545, and the Intramural Research Program of the National Institutes of Allergy and Infectious Diseases (NIAID) supported this work. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.