A method to produce a chimeric protein having a Flavivirus backbone and portions dengue virus is provided. The Flavivirus envelope protein, such as from yellow fever virus 17D vaccine strain, is modified replacing amino acids surrounding the fusion loop of the Flavivirus backbone with corresponding amino acids from the dengue virus envelope protein. The chimeric protein is useful as a vaccine to stimulate an immune response against DENV infection, thereby producing broadly neutralizing (protective) antibodies against dengue virus and reduce the induction of non-neutralizing antibodies that will cause enhancement.
