EMD-28056
Venezuelan equine encephalitis virus-like particle in complex with Fab SKT05
EMD-28056
Single-particle4.1 Å
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Map released: 19/07/2023
Last modified: 19/07/2023
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
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.
Sutton MS,
Pletnev S,
Callahan V,
Ko S,
Tsybovsky Y,
Bylund T,
Casner RG,
Cerutti G,
Gardner CL,
Guirguis V,
Verardi R,
Zhang B,
Ambrozak D,
Beddall M,
Lei H,
Yang ES,
Liu T,
Henry AR,
Rawi R,
Schon A,
Schramm CA,
Shen CH,
Shi W,
Stephens T,
Yang Y,
Florez MB,
Ledgerwood JE,
Burke CW,
Shapiro L,
Fox JM,
Kwong PD,
Roederer M
(2023) Cell , 186 , 2672 - 2689.e25
(2023) Cell , 186 , 2672 - 2689.e25
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.
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.