The disclosure provides a tetravalent Dengue virus vaccine, and methods of inducing a immune response against a Flavivirus such as Dengue virus 1-4 using the vaccine. The disclosure also provides methods of making a vaccine by introducing into a host cell a transgene that encodes a protein comprising Dengue domain III polypeptides, or, by purified dill polypeptides specific for Dengue serotypes 1-4, Yellow Fever Virus, West Nile Virus, Japanese Encephalitis Virus, and Flaviviruses.