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

• Published in: Cancers Vol. 10; no. 4; p. 112
• Main Authors: Tanner, Jerome E, Hu, Jing, Alfieri, Caroline
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 09.04.2018; MDPI
• Subjects: Alternative splicing; Cell culture; Cell proliferation; Epitopes; Epstein-Barr virus; Immunoglobulin G; Infections; Lymphocytes; Lymphocytes B; Monoclonal antibodies; Posttransplant lymphoproliferative disorders; Virions; Epstein-Barr virus; complementarity determining region; homology modeling; glycoprotein 220; glycoprotein 350; humanized antibody
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers10040112

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.