EMD-27390

Single-particle
4.1 Å
EMD-27390 Deposition: 20/06/2022
Map released: 05/07/2023
Last modified: 09/10/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-27390

Cryo-EM Structure of Western Equine Encephalitis Virus VLP in complex with SKW19 fab

EMD-27390

Single-particle
4.1 Å
EMD-27390 Deposition: 20/06/2022
Map released: 05/07/2023
Last modified: 09/10/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Western equine encephalitis virus, Homo sapiens, Homo sapiens
Sample: Homo sapiens
Fitted models: 8ded (Avg. Q-score: 0.363)

Deposition Authors: Pletnev S, Tsybovsky Y, Verardi R, Roedeger M, Kwong P
Vaccine elicitation and structural basis for antibody protection against alphaviruses.
PUBMED: 37295404
DOI: doi:10.1016/j.cell.2023.05.019
ISSN: 1097-4172
Abstract:
Alphaviruses are RNA viruses that represent emerging public health threats. To identify protective antibodies, we immunized macaques with a mixture of western, eastern, and Venezuelan equine encephalitis virus-like particles (VLPs), a regimen that protects against aerosol challenge with all three viruses. Single- and triple-virus-specific antibodies were isolated, and we identified 21 unique binding groups. Cryo-EM structures revealed that broad VLP binding inversely correlated with sequence and conformational variability. One triple-specific antibody, SKT05, bound proximal to the fusion peptide and neutralized all three Env-pseudotyped encephalitic alphaviruses by using different symmetry elements for recognition across VLPs. Neutralization in other assays (e.g., chimeric Sindbis virus) yielded variable results. SKT05 bound backbone atoms of sequence-diverse residues, enabling broad recognition despite sequence variability; accordingly, SKT05 protected mice against Venezuelan equine encephalitis virus, chikungunya virus, and Ross River virus challenges. Thus, a single vaccine-elicited antibody can protect in vivo against a broad range of alphaviruses.