Development of a highly protective combination monoclonal antibody therapy against Chikungunya virus.

Pankaj Pal; Kimberly A Dowd; James D Brien; Melissa A Edeling; Sergey Gorlatov; Syd Johnson; Iris Lee; Wataru Akahata; Gary J Nabel; Mareike KS Richter; Jolanda M Smit; Daved H Fremont; Theodore C Pierson; Mark T Heise; Michael S Diamond

Journal article

Development of a highly protective combination monoclonal antibody therapy against Chikungunya virus.

Pankaj Pal, Kimberly A Dowd, James D Brien, Melissa A Edeling, Sergey Gorlatov, Syd Johnson, Iris Lee, Wataru Akahata, Gary J Nabel, Mareike KS Richter, Jolanda M Smit, Daved H Fremont, Theodore C Pierson, Mark T Heise, Michael S Diamond

PLoS Pathog | Published : 2013

DOI: 10.1371/journal.ppat.1003312

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 vi..

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