Neutralization of Japanese Encephalitis Virus by heme-induced broadly reactive human monoclonal antibody

Nimesh Gupta,Maxime Lecerf,Srinivas V Kaveri,Tobias Scheel,Mélissanne De Wispelaere,Sudhanshu Vrati,Manjula Kalia,Jordan D Dimitrov,Claudia Berek,Sébastien Lacroix-Desmazes,Philippe Desprès

doi:10.1038/srep16248

Abstract

Geographical expansion and re-emerging new genotypes of the Japanese encephalitis virus (JEV) require the development of novel therapeutic approaches. Here, we studied a non-conventional approach for antibody therapy and show that, upon exposure to heme, a fraction of natural human immunoglobulins acquires high-affinity reactivity with the antigenic domain-III of JEV E glycoprotein. These JEV-reactive antibodies exhibited neutralizing activity against recently dominant JEV genotypes. This study opens new therapeutic options for Japanese encephalitis.

Highlights

The appearance of new highly virulent genotypes of Japanese encephalitis virus (JEV) is a growing cause of concern[1,2]
We analyzed a panel of 97 human recombinant monoclonal IgG1, cloned from different subpopulations of B cells isolated from the synovial tissue of patients with rheumatoid arthritis[22]
Further analyses of the characteristics of the variable region sequences of the immunoglobulins revealed that Abs, that acquired reactivity towards JEV E upon heme exposure have significantly lower number of somatic mutations (Fisher’s exact test P = 0.01) (Fig. 1C)

Summary

OPEN Neutralization of Japanese

Encephalitis Virus by hemereceived: 16 July 2015 accepted: 12 October 2015 Published: 06 November 2015 induced broadly reactive human monoclonal antibody. We studied a non-conventional approach for antibody therapy and show that, upon exposure to heme, a fraction of natural human immunoglobulins acquires high-affinity reactivity with the antigenic domain-III of JEV E glycoprotein. Following an infected mosquito bite, the virus replicates at low levels in the spleen and spreads by haematogenous route to other parts of the body including the central nervous system In this early phase, the immune response efficiency determines disease outcome[4]. JE has an incubation period of 5 to 15 days and non-specific symptoms may last for up to 6 days It is uncertain whether the mere targeting of the virus using JEV-specific Abs would be therapeutically efficient. Abs with inducible polyreactivity may represent an appropriate therapeutic tool for JEV-mediated disease

Results and Discussion

Methods

Author Contributions

Additional Information