DENGUE VIRUS E-GLYCOPROTEIN POLYPEPTIDES CONTAINING MUTATIONS THAT ELIMINATE IMMUNODOMINANT CROSS-REACTIVE EPITOPES

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 positions 106, 107, 310 and 31 1, and either position 364 or position 389 of dengue serotype 1 (DENV- l) E- glycoprotein. The provided E-glycoprotein polypeptides optionally further include mutations corresponding to positions 468, 478, 482 and 487 of DENV-1 E-glycoprotein.