THE UNITED STATES OF AMERICA; AS REPRESENTED BY THE SECRETARY; DEPARTMENT OF HEALTH AND HUMAN SERVICES
发明人:
PLETNEV, ALEXANDER, G.,MURPHY, BRIAN, R.,ENGEL, AMBER, R.
申请号：
EP10781321
公开号：
EP2435572A4
申请日:
2010.05.28
申请国别(地区):
EP
年份:
2013
代理人:
摘要：
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.
