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Comparative Prime-Boost Vaccinations Using Semliki Forest Virus, Adenovirus, and ALVAC Vectors Demonstrate Differences in the Generation of a Protective Central Memory CTL Response against the P815 Tumor¹

Tanja I. Näslund^*, Catherine Uyttenhove^,, Eva K. L. Nordström^*, Didier Colau^,, Guy Warnier^,, Mikael Jondal^*, Benoît J. Van den Eynde^, and Peter Liljeström^2,*

^* Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden; Ludwig Institute for Cancer Research, Brussels Branch, Brussels, Belgium; and Université catholique de Louvain, Brussels, Belgium

Tumor-specific Ags are potential target molecules in the therapeutic treatment of cancer. One way to elicit potent immune responses against these Ags is to use recombinant viruses, which activate both the innate and the adaptive arms of the immune system. In this study, we have compared Semliki Forest virus (SFV), adenovirus, and ALVAC (poxvirus) vectors for their capacity to induce CD8⁺ T cell responses against the P1A tumor Ag and to elicit protection against subsequent challenge injection of P1A-expressing P815 tumor cells in DBA/2 mice. Both homologous and heterologous prime-boost regimens were studied. In most cases, both higher CD8⁺ T cell responses and better tumor protections were observed in mice immunized with heterologous prime-boost regimens, suggesting that the combination of different viral vectors is beneficial for the induction of an effective immune response. However, homologous immunization with SFV provided potent tumor protection despite a rather moderate primary CD8⁺ T cell response as compared with mice immunized with recombinant adenovirus. SFV-immunized mice showed a rapid and more extensive expansion of P1A-specific CD8⁺ T cells in the tumor-draining lymph node after tumor challenge and had a higher frequency of CD62L⁺ P1A-specific T cells in the blood, spleen, and lymph nodes as compared with adenoimmunized mice. Our results indicate that not only the magnitude but in particular the quality of the CD8⁺ T cell response correlates with tumor protection.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by the Swedish Research Council, the European Union 5th Framework Program, the European Community (QLGA-CT-2000-60013), and the Fondation contre le Cancer.

² Address correspondence and reprint requests to Dr. Peter Liljeström, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Nobels väg 16, Box 280, 17177 Stockholm, Sweden. E-mail address: Peter.Liljestrom{at}ki.se

³ Abbreviations used in this paper: DC, dendritic cell; LN, lymph node; MLTC, mixed lymphocyte tumor culture; P1A_t, P1A truncated; SFV, Semliki Forest virus; T_CM, central memory T cell; T_EM, effector memory T cell.