Structural highlights
FunctionPublication Abstract from PubMedAlphaviruses 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. 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 Cell. 2023 Jun 8;186(12):2672-2689.e25. doi: 10.1016/j.cell.2023.05.019. Epub , 2023 Jun 8. PMID:37295404[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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