8DUL

Cryo-EM Structure of Antibody SKT05 in complex with Western Equine Encephalitis Virus spike (local refinement from VLP particles)

Summary for 8DUL

• Entry DOI: 10.2210/pdb8dul/pdb
• EMDB information: 27722
• Descriptor: Spike glycoprotein E2, Spike glycoprotein E1, Antibody Fab SKT05 heavy chain, ... (6 entities in total)
• Functional Keywords: antibody, skt05, western equine encephalitis virus, broadly neutralizing, immune system
• Biological source: Western equine encephalitis virus; More
• Total number of polymer chains: 8
• Total formula weight: 345547.66

Authors

Cerutti, G.,Verardi, R.,Roederer, M.,Shapiro, L. (deposition date: 2022-07-27, release date: 2023-07-05)

Primary citation

Sutton, M.S.,Pletnev, S.,Callahan, V.,Ko, S.,Tsybovsky, Y.,Bylund, T.,Casner, R.G.,Cerutti, G.,Gardner, C.L.,Guirguis, V.,Verardi, R.,Zhang, B.,Ambrozak, D.,Beddall, M.,Lei, H.,Yang, E.S.,Liu, T.,Henry, A.R.,Rawi, R.,Schon, A.,Schramm, C.A.,Shen, C.H.,Shi, W.,Stephens, T.,Yang, Y.,Florez, M.B.,Ledgerwood, J.E.,Burke, C.W.,Shapiro, L.,Fox, J.M.,Kwong, P.D.,Roederer, M.
Vaccine elicitation and structural basis for antibody protection against alphaviruses.
Cell, 186:2672-2689.e25, 2023

PubMed 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.

PubMed: 37295404
DOI: 10.1016/j.cell.2023.05.019

Experimental method

ELECTRON MICROSCOPY (4.17 Å)