EMD-28056

Single-particle
4.1 Å
EMD-28056 Deposition: 07/09/2022
Map released: 19/07/2023
Last modified: 19/07/2023
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-28056

Venezuelan equine encephalitis virus-like particle in complex with Fab SKT05

EMD-28056

Single-particle
4.1 Å
EMD-28056 Deposition: 07/09/2022
Map released: 19/07/2023
Last modified: 19/07/2023
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Venezuelan equine encephalitis virus, Macaca fascicularis
Sample: Complex between Venezuelan equine encephalitis virus-like particle and Fab SKT05

Deposition Authors: Tsybovsky Y, Pletnev S, Verardi R, Roederer M, Kwong PD
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.