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Cancers 2018, 10(4), 112; https://doi.org/10.3390/cancers10040112

Construction and Characterization of a Humanized Anti-Epstein-Barr Virus gp350 Antibody with Neutralizing Activity in Cell Culture

1
Laboratory of Viral Pathogenesis, Research Centre, CHU Sainte-Justine, Montréal, QC H3T 1C5, Canada
2
Department of Microbiology, Infectiology and Immunology, University of Montreal, 3175 Côte Ste-Catherine Road, Montreal, QC H3T 1C5, Canada
*
Author to whom correspondence should be addressed.
Received: 28 February 2018 / Revised: 30 March 2018 / Accepted: 4 April 2018 / Published: 9 April 2018
(This article belongs to the Special Issue Epstein–Barr Virus Associated Cancers)
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Abstract

Acute Epstein-Barr virus (EBV) infection in immunosuppressed transplant patients can give rise to a malignant B-cell proliferation known as post-transplant lymphoproliferative disease (PTLD). The EBV major virion surface glycoprotein (gp)350 is a principal target of naturally occurring neutralizing antibodies and is viewed as the best target to prevent acute infection and PTLD in at-risk transplant recipients. We have constructed a humanized (hu) version of the murine anti-gp350 neutralizing monoclonal antibody 72a1. The hu72a1 IgG1 antibody displayed no significant anti-mouse activity, recognized both gp350 and its splice variant gp220 as well as a gp350 peptide that was shown to constitute the principal EBV gp350 neutralizing epitope when tested in immunoassays. Hu72a1 antibody blocked in vitro EBV infection of B cells at a level which equaled that of a mouse-human chimeric 72a1 antibody construct. This work provides a further structural and immunological understanding of the 72a1 antibody interaction with EBV gp350, and constitutes a launch point for future anti-EBV therapeutic antibodies designed to block EBV infection and prevent PTLD while eliminating the deleterious antigenic murine features of the original 72a1 antibody. View Full-Text
Keywords: Epstein-Barr virus; humanized antibody; glycoprotein 350; glycoprotein 220; homology modeling; complementarity determining region Epstein-Barr virus; humanized antibody; glycoprotein 350; glycoprotein 220; homology modeling; complementarity determining region
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Tanner, J.E.; Hu, J.; Alfieri, C. Construction and Characterization of a Humanized Anti-Epstein-Barr Virus gp350 Antibody with Neutralizing Activity in Cell Culture. Cancers 2018, 10, 112.

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