YELLOW FEVER VIRUS NS5 MUTANTS AS FLAVIVIRUS VACCINE CANDIDATES

摘要

Provided herein are attenuated yellow fever viruses comprising a genome that encodes a mutated NS5 protein comprising a deletion of the first 10 amino acids or an amino acid substitution of another residue (e.g., arginine or alanine) for the first N-terminal lysine residue. In one embodiment, the attenuated YFV is genetically engineered to also express a heterologous antigen. The heterologous antigen can be any antigen, such as an antigen from a different YFV strain, from a different flavivirus, or from a pathogen, a cancer-associated antigen, or an allergy- related antigen. The attenuated YFVs can be engineered to express the heterologous antigen and mutated NS5 protein using techniques known in the art. Also provided herein are vaccines comprising an attenuated YFV described herein and methods of immunizing a subject (e.g., an animal such as a non-human animal or human) or preventing a disease using the YFV.