Monoclonal Anti-Claudin 1 Antibodies Prevent Hepatitis C Virus Infection of Primary Human Hepatocytes

Novel human anti-claudin 1 mAbs inhibit hepatitis C virus infection and may synergize with anti-SRB1 mAb

“…The ability of anti-CLDN-1 human mAbs to inhibit infection by different HCV isolates was not unexpected and was in line with previous observations made with rat and mouse anti-CLDN-1 antibodies (Fofana et al, 2010;Fukasawa et al, 2015;Mailly et al, 2015;Yamashita et al, 2015). Most importantly, mAbs B9X and D10X displayed binding affinity for cell-displayed CLDN-1 and IC 50 values comparable with the rat anti-CLDN-1 mAb OM-7D3, which was recently shown to prevent HCV infection and to clear persistent infection in a human liver-chimeric mouse model without detectable toxicity .…”

“…The tight junction protein CLDN-1 is an essential receptor for HCV infection of human hepatocytes in vitro and in vivo (Fofana et al, 2010;Mailly et al, 2015). Recently, it was shown that rat, mouse and human/mouse hybrid mAbs are effective against HCV infection in vitro and in vivo without detectable toxicity when administered to human liver-chimeric mice Mailly et al, 2015).…”

“…In particular, we previously showed that the human anti-SRB1 mAb C-1671 completely prevents infection and intrahepatic spread of multiple HCV genotypes in vivo in human liver-chimeric mice (Meuleman et al, 2012). Human mAbs against CLDN-1 and OCLN have not been reported yet, but rat, mouse and mouse/human chimeric anti-CLDN-1 antibodies were found to efficiently inhibit infection by HCV of major genotypes in cell culture (Fofana et al, 2010;Yamashita et al, 2015) and some of them eliminate chronic HCV infection without detectable toxicity when administered to human liver-chimeric mice Mailly et al, 2015).…”

Enfermé dehors

“…Notre laboratoire a produit et caracté-risé différents anticorps monoclonaux dirigés contre la claudine-1 (CLDN1), et l'un d'entre eux, le clone OM-7D3-B3, s'est montré particulièrement efficace in vitro pour inhiber l'entrée du VHC [10]. Nous avons utilisé le modèle de souris chimériques afin de tester l'efficacité de cet anticorps anti-CLDN1 in vivo [11].…”

Recent Advances in Claudin-Targeting Technology

“…47) another group created anti-cL-1 antibodies that prevented the infection of human hepatocytes by hepatitis c virus. 48) although these successes will encourage further development of cL antibodies, the high costs associated with this process likely will limit the clinical application of these reagents to the treatment of widespread diseases such as cancer and hepatitis c. In addition, cL-binding chemicals or peptides must be created to capitalize on the capacity for noninvasive administration and drug delivery to peripheral and central neurons through modulation of cLs. To this end, the three-dimensional structures of cLs need to be determined, and the process of developing antibodies to cLs may yield insights into their solubilization and crystallization.…”