Title :

A Protective Monoclonal Antibody Targets a Site of Vulnerability on the Surface of Rift Valley Fever Virus.

Abstract :

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, E.R., Krumm, S.A., Raghwani, J., Halldorsson, S., Elliott, A., Graham, V.A.,
Koudriakova, E., Harlos, K., Wright, D., Warimwe, G.M., Brennan, B., Huiskonen, J.T., Dowall,
S.D., Elliott, R.M., Pybus, O.G., Burton, D.R., Hewson, R., Doores, K.J., Bowden, T.A.

PubMed link :

Journals :

Cell Reports. 2018