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-Structure paper
タイトル | Vaccine elicitation and structural basis for antibody protection against alphaviruses. |
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ジャーナル・号・ページ | Cell, Vol. 186, Issue 12, Page 2672-2689.e25, Year 2023 |
掲載日 | 2023年6月8日 |
著者 | Matthew S Sutton / Sergei Pletnev / Victoria Callahan / Sungyoul Ko / Yaroslav Tsybovsky / Tatsiana Bylund / Ryan G Casner / Gabriele Cerutti / Christina L Gardner / Veronica Guirguis / Raffaello Verardi / Baoshan Zhang / David Ambrozak / Margaret Beddall / Hong Lei / Eun Sung Yang / Tracy Liu / Amy R Henry / Reda Rawi / Arne Schön / Chaim A Schramm / Chen-Hsiang Shen / Wei Shi / Tyler Stephens / Yongping Yang / Maria Burgos Florez / Julie E Ledgerwood / Crystal W Burke / Lawrence Shapiro / Julie M Fox / Peter D Kwong / Mario Roederer / |
PubMed 要旨 | 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 ...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. |
リンク | Cell / PubMed:37295404 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.3 - 7.0 Å |
構造データ | EMDB-27389, PDB-8dec: EMDB-27390, PDB-8ded: EMDB-27391, PDB-8dee: EMDB-27392, PDB-8def: EMDB-27395, PDB-8deq: EMDB-27396, PDB-8der: EMDB-27722, PDB-8dul: EMDB-27723, PDB-8dun: EMDB-27757, PDB-8dwo: EMDB-28056: Venezuelan equine encephalitis virus-like particle in complex with Fab SKT05 EMDB-28058: Venezuelan equine encephalitis virus-like particle in complex with Fab SKT05, local refinement EMDB-28059: Venezuelan equine encephalitis virus-like particle in complex with Fab SKT20 EMDB-28060: Venezuelan equine encephalitis virus-like particle in complex with Fab SKT-20, local refinement EMDB-28115: Western Equine Encephalitis Virus-Like Particle in Complex with SKW19 Fab EMDB-28116: Western Equine Encephalitis Virus-Like Particle in Complex with SKW24 Fab EMDB-28117: Eastern Equine Encephalitis Virus-Like Particle in Complex with SKE26 Fab EMDB-28118: Cryo-EM structure of Antibody SKW11 in complex with Western Equine Encephalitis Virus-Like Particle EMDB-28119: Cryo-EM structure of Antibody SKT05 in complex with Western Equine Encephalitis Virus-like Particle EMDB-28187: Cryo-EM I1 reconstruction of antibody SKV09 in complex with VEEV alphavirus VLP EMDB-28188: Cryo-EM I1 reconstruction of antibody SKV16 in complex with VEEV alphavirus VLP |
化合物 | ChemComp-NAG: |
由来 |
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キーワード | VIRUS LIKE PARTICLE / Western Equine Encephalitis Virus / Virus-Like Particle / VIRUS/IMMUNE SYSTEM / antibody / VLP-Fab complex / VIRUS-IMMUNE SYSTEM complex / VIRAL PROTEIN / antibody alphavirus VEEV spike trimer glycoprotein / IMMUNE SYSTEM / SKT05 / broadly neutralizing / SKW11 / Eastern Equine Encephalitis virus / virus-fab complex / VIRUS LIKE PARTICLE/IMMUNE SYSTEM / Venezuelan equine encephalitis virus / neutralizing antibody / VEEV / VIRUS LIKE PARTICLE-IMMUNE SYSTEM complex |