8EEU

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

Summary for 8EEU

• Entry DOI: 10.2210/pdb8eeu/pdb
• EMDB information: 28056 28058
• Descriptor: Coat protein, Fab SKT05 heavy chain, Fab SKT05 light chain (3 entities in total)
• Functional Keywords: venezuelan equine encephalitis virus, neutralizing antibody, veev, virus like particle-immune system complex, virus like particle/immune system
• Biological source: Venezuelan equine encephalitis virus; More
• Total number of polymer chains: 8
• Total formula weight: 880731.55

Authors

Tsybovsky, Y.,Pletnev, S.,Verardi, R.,Roederer, M.,Kwong, P.D. (deposition date: 2022-09-07, release date: 2023-07-19)

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 (3.5 Å)