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Journal of Virology, October 2000, p. 9197-9205, Vol. 74, No. 19
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Recombinant Yellow Fever Viruses Are Effective Therapeutic Vaccines for Treatment of Murine Experimental Solid Tumors and Pulmonary Metastases†

Andrés McAllister,Dagger Alejandra E. Arbetman, Stefanie Mandl, Claudia Peña-Rossi,§ and Raul Andino*

Department of Microbiology and Immunology, University of California, San Francisco, California 94143-0414

Received 13 April 2000/Accepted 10 July 2000

We have genetically engineered an attenuated yellow fever (YF) virus to carry and express foreign antigenic sequences and evaluated the potential of this type of recombinant virus to serve as a safe and effective tumor vaccine. Live-attenuated YF vaccine is one of the most effective viral vaccines available today. Important advantages include its ability to induce long-lasting immunity, its safety, its affordability, and its documented efficacy. In this study, recombinant live-attenuated (strain 17D) YF viruses were constructed to express a cytotoxic T-lymphocyte epitope derived from chicken ovalbumin (SIINFEKL). These recombinant viruses replicated comparably to the 17D vaccine strain in cell culture and stably expressed the ovalbumin antigen, and infected cells presented the antigen in the context of major histocompatibility complex class I. Inoculation of mice with recombinant YF virus elicited SIINFEKL-specific CD8+ lymphocytes and induced protective immunity against challenge with lethal doses of malignant melanoma cells expressing ovalbumin. Furthermore, active immunotherapy with recombinant YF viruses induced regression of established solid tumors and pulmonary metastases. Thus, recombinant YF viruses are attractive viral vaccine vector candidates for the development of therapeutic anticancer vaccines.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, Box 0414, University of California, San Francisco, CA 94143-0414. Phone: (415) 502-6358. Fax: (415) 476-0939. E-mail: andino{at}itsa.ucsf.edu.

dagger Dedicated to the memory of Rob Sadler (1962-1999).

Dagger Present address: Centre d'Immunologie Pierre Fabre, St. Julien en Genevois Cedex, 74164 France.

§ Present address: Serono Pharmaceutical Research Institute, 1228 Plan-les-Ouates, Switzerland.

Journal of Virology, October 2000, p. 9197-9205, Vol. 74, No. 19
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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