Structural basis for recognition of Rift Valley fever virus Gn protein by a human neutralizing monoclonal antibody with a kappa light chain

Paesen, GC; Chapman, NS; Westover, JB; McMillen, CM; Kuzmina, NA; Dews, EA; Myers, L; Stass, R; Montgomery, JM; Bukreyev, A; Hartman, AL; Gowen, BB; Crowe, JE; Bowden, TA

Journal article

Structural basis for recognition of Rift Valley fever virus Gn protein by a human neutralizing monoclonal antibody with a kappa light chain

Abstract:: Rift Valley fever virus (RVFV) poses a continued threat to human health and animal husbandry. Two neutralizing and protective human monoclonal antibodies (mAbs), RVFV-268 and RVFV-379, exhibit similar affinities and epitope footprints on the Gn glycoprotein component of the RVFV Gn-Gc capsomeric lattice. Here, we define fine details of the biophysical determinants of Gn recognition used by RVFV human monoclonal antibodies through studying an antibody encoded by a set of recombined genes not previously identified in RVFV antibodies. We find that RVFV-379 exhibits a larger footprint than that observed for RVFV-268 and other antibodies targeting the same region, which involves major contributions of both the light and heavy chains. RVFV-379 also uses an oblique angle of approach towards the virion surface that contrasts with the perpendicular angle of engagement observed for some other potently neutralizing human mAbs. Further, consistent with amino acid sequence variation within and proximal to the RVFV-379 epitope, in vitro neutralization screening reveals a limited degree of neutralization breadth across prevalent RVFV strains, suggesting that RVFV has fewer functional constraints at this region of the virus envelope. By dissecting the molecular determinants of mAb recognition of Gn, this integrated analysis refines strategies needed for the rational design of vaccines that can elicit a potent and species-wide protective antibody immune response to this important re-emerging pathogen.

Publication status:: Published

Peer review status:: Peer reviewed

Actions

Email

Email this record

Send the bibliographic details of this record to your email address.

Your Email
Please enter the email address that the record information will be sent to.

-
Your message (optional)
Please add any additional information to be included within the email.
Share
Cite

Cite this record

APA Style

Paesen, G. C., Chapman, N. S., Westover, J. B., McMillen, C. M., Kuzmina, N. A., Dews, E. A., Myers, L., Stass, R., Montgomery, J. M., Bukreyev, A., Hartman, A. L., Gowen, B. B., Crowe, J. E., & Bowden, T. A. (2026). Structural basis for recognition of Rift Valley fever virus Gn protein by a human neutralizing monoclonal antibody with a kappa light chain. PLoS Pathogens, 22(2), e1013926.

MLA Style

Paesen, GC, et al. “Structural Basis for Recognition of Rift Valley Fever Virus Gn Protein by a Human Neutralizing Monoclonal Antibody with a Kappa Light Chain.” PLoS Pathogens, vol. 22, no. 2, 2026, p. e1013926.

Chicago Style

Paesen, GC, NS Chapman, JB Westover, et al. 2026. “Structural Basis for Recognition of Rift Valley Fever Virus Gn Protein by a Human Neutralizing Monoclonal Antibody with a Kappa Light Chain.” PLoS Pathogens 22 (2): e1013926.
Print