5AAW

Structure of a redesigned cross-reactive antibody to dengue virus with increased in vivo potency

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5AAW の概要

• エントリーDOI: 10.2210/pdb5aaw/pdb
• 関連するPDBエントリー: 5AAM
• 分子名称: SCFV513, DENGUE SEROTYPE 4 ENVELOPE PROTEIN DOMAIN 3 (3 entities in total)
• 機能のキーワード: viral protein, scfv dengue antibody envelope domain iii
• 由来する生物種: MUS MUSCULUS (HOUSE MOUSE); 詳細
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 240720.29

構造登録者

Wong, Y.,Robinson, L.,Lescar, J.,Sasisekharan, R. (登録日: 2015-07-30, 公開日: 2015-09-30, 最終更新日: 2024-11-13)

主引用文献

Robinson, L.N.,Tharakaraman, K.,Rowley, K.J.,Costa, V.V.,Chan, K.R.,Wong, Y.H.,Ong, L.C.,Tan, H.C.,Koch, T.,Cain, D.,Kirloskar, R.,Viswanathan, K.,Liew, C.W.,Tissire, H.,Ramakrishnan, B.,Myette, J.R.,Babcock, G.J.,Sasisekharan, V.,Alonso, S.,Chen, J.,Lescar, J.,Shriver, Z.,Ooi, E.E.,Sasisekharan, R.
Structure-Guided Design of an Anti-Dengue Antibody Directed to a Non-Immunodominant Epitope.
Cell(Cambridge,Mass.), 162:493-, 2015

PubMed Abstract: Dengue is the most common vector-borne viral disease, causing nearly 400 million infections yearly. Currently there are no approved therapies. Antibody epitopes that elicit weak humoral responses may not be accessible by conventional B cell panning methods. To demonstrate an alternative strategy to generating a therapeutic antibody, we employed a non-immunodominant, but functionally relevant, epitope in domain III of the E protein, and engineered by structure-guided methods an antibody directed to it. The resulting antibody, Ab513, exhibits high-affinity binding to, and broadly neutralizes, multiple genotypes within all four serotypes. To assess therapeutic relevance of Ab513, activity against important human clinical features of dengue was investigated. Ab513 mitigates thrombocytopenia in a humanized mouse model, resolves vascular leakage, reduces viremia to nearly undetectable levels, and protects mice in a maternal transfer model of lethal antibody-mediated enhancement. The results demonstrate that Ab513 may reduce the public health burden from dengue.

PubMed: 26189681
DOI: 10.1016/J.CELL.2015.06.057

実験手法

X-RAY DIFFRACTION (3.27 Å)