A protective monoclonal antibody targets a site of vulnerability on the surface of Rift Valley fever virus

Journal article

The Gn subcomponent of the Gn-Gc assembly that envelopes the human and animal pathogen, Rift Valley fever virus (RVFV), is a primary target of the neutralizing antibody response. To better understand the molecular basis for immune recognition, we raised a class of neutralizing monoclonal antibodies (nAbs) against RVFV Gn, which exhibited protective efficacy in a mouse infection model. Structural characterization revealed that these nAbs were directed to the membrane-distal domain of RVFV Gn and likely prevented virus entry into a host cell by blocking fusogenic rearrangements of the Gn-Gc lattice. Genome sequence analysis confirmed that this region of the RVFV Gn-Gc assembly was under selective pressure and constituted a site of vulnerability on the virion surface. These data provide a blueprint for the rational design of immunotherapeutics and vaccines capable of preventing RVFV infection and a model for understanding Ab-mediated neutralization of bunyaviruses more generally.

Authors: Allen, ER; Krumm, SA; Raghwani, J; Halldorsson, S; Elliott, A

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Elsevier
• Journal: Cell Reports
• Volume: 25
• Issue: 13
• Pages: 3750-3758
• Publication date: 2018-12-26
• Acceptance date: 2018-11-29
• DOI: 10.1016/j.celrep.2018.12.001
• EISSN: 2211-1247
• ISSN: 2211-1247
• Pmid: 30590046
• Language: English
• Keywords: neutralization; structure; antiviral; vaccine; phlebovirus; antibody; virus-host interactions; Rift Valley fever virus; immune response; bunyavirus