US Patent:
20120076821, Mar 29, 2012
Inventors:
Alexander G. Pletnev - Gaithersburg MD, US
Brian R. Murphy - Bethesda MD, US
Amber R. Engel - Gaithersburg MD, US
International Classification:
A61K 39/12
A61P 37/04
C12N 7/01
Abstract:
Disclosed herein are chimeric TBEV/DEN4 flaviviruses including a first nucleic acid molecule including a 5′ non-coding region (NCR) from a DEN4 virus, a nucleic acid encoding a C protein and non-structural proteins from a DEN4 virus, and a 3′ NCR from a DEN4 virus, wherein nonstructural protein NS4B includes a phenylalanine at amino acid position 112, nonstructural protein NS5 includes an alanine at amino acid position 654 and an alanine at amino acid position 655, and the 3′ NCR includes a deletion of nucleotides 10478-10507. The chimeric construct also includes a second nucleic acid molecule, which is operably linked to the first nucleic acid molecule, encoding a prM protein and an E protein from a TBEV, wherein the E protein includes an amino acid substitution that differs from the wild type TBEV at amino acid position 315 and a tryptophan at amino acid position 240. Also disclosed are methods of eliciting an immune response using the disclosed TBEV/DEN4 chimeric flaviviruses and immunogenic compositions including the disclosed chimeric flaviviruses and a pharmaceutically acceptable carrier.