Recombinant yellow fever viruses are effective therapeutic vaccines for treatment of murine experimental solid tumors and pulmonary metastases

We have genetically engineered an attenuated yellow fever (YF) virus to car ry and express foreign antigenic sequences and evaluated the potential of t his type of recombinant virus to serve as a safe and effective tumor vaccin e. Live-attenuated YF vaccine is one of the most effective viral vaccines a vailable today. Important advantages include its ability to induce long-las ting immunity, its safety, its affordability, and its documented efficacy. In this study, recombinant live-attenuated (strain 17D) YF viruses were con structed to express a cytotoxic T-lymphocyte epitope derived from chicken o valbumin (SIINFEKL). These recombinant viruses replicated comparably to the 17D vaccine strain in cell culture and stably expressed the ovalbumin anti gen, and infected cells presented the antigen in the contest of major histo compatibility complex class I. Inoculation of mice with recombinant YF viru s elicited SIINFEKL-specific CD8(+) lymphocytes and induced protective immu nity against challenge with lethal doses of malignant melanoma cells expres sing ovalbumin. Furthermore, active immunotherapy with recombinant YF virus es induced regression of established solid tumors and pulmonary metastases. Thus, recombinant YF viruses are attractive viral vaccine vector candidate s for the development of therapeutic anticancer vaccines.