Characterization of antibody interactions with the G protein of vesicular stomatitis virus Indiana strain and other vesiculovirus G proteins

Journal article

Vesicular stomatitis virus Indiana strain G protein (VSVind.G) is the most commonly used envelope glycoprotein to pseudotype lentiviral vectors (LV) for experimental and clinical applications. Recently, G proteins derived from other vesiculoviruses (VesG), for example, Cocal virus, have been proposed as alternative LV envelopes with possible advantages over VSVind.G. Well-characterized antibodies that recognize VesG will be useful for vesiculovirus research, development of G protein-containing advanced therapy medicinal products (ATMPs), and deployment of VSVind-based vaccine vectors. Here, we show that one commercially available monoclonal antibody, 8G5F11, binds to and neutralizes G proteins from three strains of VSV, as well as Cocal and Maraba viruses, whereas the other commercially available monoclonal anti-VSVind.G antibody, IE9F9, binds to and neutralizes only VSVind.G. Using a combination of G protein chimeras and site-directed mutations, we mapped the binding epitopes of IE9F9 and 8G5F11 on VSVind.G. IE9F9 binds close to the receptor binding site and competes with soluble low-density lipoprotein receptor (LDLR) for binding to VSVind.G, explaining its mechanism of neutralization. In contrast, 8G5F11 binds close to a region known to undergo conformational changes when the G protein moves to its postfusion structure, and we propose that 8G5F11 cross-neutralizes VesGs by inhibiting this.

Authors: Munis, A; Tijani, M; Hassall, M; Mattiuzzo, G; Collins, M

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: American Society for Microbiology
• Journal: Journal of Virology
• Volume: 92
• Issue: 23
• Pages: e00900-18
• Publication date: 2018-11-12
• Acceptance date: 2018-09-06
• DOI: 10.1128/JVI.00900-18
• EISSN: 1098-5514
• ISSN: 0022-538X
• Keywords: monoclonal antibodies; vesiculovirus; neutralizing antibodies; VSV