公开(公告)号：EP2768847A1

公开(公告)日：2014-08-27

申请号：EP12841016.4

申请日：2012-10-18

申请人： The Government of the United States of America as Represented by the Secretary of the Department of Health and Human Services

发明人： CHANG, Gwong-jen, J. ,  CRILL, Wayne, D. ,  HUGHES, Holly, R. ,  DAVIS, Brent, S.

IPC分类号： C07K14/18 ,  C12N15/40 ,  A61K39/12 ,  A61K39/295

CPC分类号： A61K39/12 ,  A61K2039/5258 ,  A61K2039/53 ,  A61K2039/57 ,  A61K2039/575 ,  A61K2039/6031 ,  A61K2039/6075 ,  A61K2039/70 ,  C07K14/005 ,  C12N7/00 ,  C12N2770/24122 ,  C12N2770/24123 ,  C12N2770/24134 ,  C12N2770/24151 ,  C12N2770/24171 ,  Y02A50/386

摘要： Described herein are dengue virus E-glycoprotein polypeptides containing mutations that eliminate immunodominant cross-reactive epitopes associated with immune enhancement. The disclosed dengue virus E-glycoproteins optionally further include mutations that introduce a strong CD4 T cell epitope. The disclosed E-glycoprotein polypeptides, or nucleic acid molecules encoding the polypeptides, can be used, for example, in monovalent or tetravalent vaccines against dengue virus. The dengue virus E-glycoprotein polypeptides have amino acid substitutions at residues corresponding to position 106, 107, 310 and 311, and either position 364 or position 389 of dengue serotype 1 (DENV-1) E-glycoprotein. The provided E-glycoprotein polypeptides optionally further include mutations corresponding to positions 468, 478, 482 and 487 of DENV-1 E-glycoprotein.