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Structural Analysis of Lineage I Lassa Virus Glycoprotein


EMSL Project ID
51800

Abstract

Lassa virus (LASV), the causative agent of Lassa hemorrhagic fever, is endemic in Western Africa, infecting over 100,000 people every year, resulting in roughly 5,000 deaths—yet no vaccines are currently available. Six genetic lineages of LASV currently circulate. Among these, Lineage I is the most difficult to neutralize and circulates throughout a conflict zone in densely populated Nigeria. The surface glycoprotein is the sole antigen expressed on the viral surface, and is therefore a critical target for antibody-mediated neutralization. I have undertaken a single particle cryo-EM analysis of the Lineage I surface glycoprotein in complex with human antibodies to understand why it is poorly neutralized and to develop better vaccines and therapeutics. For this study, I have produced grids of the Lineage I surface glycoprotein in complex with the Fab fragment belonging to an antibody we engineered for more potent neutralization across all six lineages.

Project Details

Start Date
2021-01-15
End Date
2021-03-17
Status
Closed

Team

Principal Investigator

Erica Saphire
Institution
La Jolla Institute for Immunology

Team Members

Tierra Buck
Institution
La Jolla Institute for Immunology

Adrian Enriquez
Institution
La Jolla Institute for Immunology

Kathryn Hastie
Institution
La Jolla Institute for Immunology