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Recombinant Semliki Forest virus vaccine vectors: the route of injection determines the localization of vector RNA and subsequent T cell response

Gene Therapy volume 8, pages 1307–1314 (2001)Cite this article

Abstract

Vectors based on Semliki Forest virus (SFV) have been widely used in vitro and in vivo to express heterologous genes in animal cells. In particular, the ability of recombinant SFV (rSFV) to elicit specific, protective immune responses in animal models suggests that rSFV may be used as a vaccine vehicle. In this study, we examined the distribution of rSFV in vivo by immunohistochemistry and RT-PCR after intravenous, intramuscular and subcutaneous injection of rSFV particles and related this to the degree of cytotoxic T lymphocyte (CTL) responses and frequency of specific T cells detected by MHC-I tetramers. We found that after i.v. injection, rSFV-RNA was distributed to a variety of different tissues, whereas it was confined locally after i.m. and s.c. injections. The persistence of the rSFV vector was transient, and no viral RNA could be detected 10 days after inoculation. All tested routes of immunization generated significant levels of antigen-specific CTL responses and increased numbers of specific CD8+T cells, as detected by tetramer binding. The distribution of antigen-specific CTLs correlated with the in vivo distribution pattern of rSFV, with a highest frequency in the spleen or local lymph node, depending on the injection route.

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Acknowledgements

The authors thank Margareta Hagelin for excellent technical assistance, and Dr M Chen and Dr E Castaños Velez for helpful discussions. This work was supported by the Swedish Cancer Research Foundation.

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Authors and Affiliations

  1. Microbiology and Tumorbiology Center, Karolinska Institutet, Stockholm, Sweden

    P Colmenero, P Berglund, T Kambayashi, P Liljeström & M Jondal

  2. Department of Vaccine Research, Swedish Institute for Infectious Disease Control, Stockholm, Sweden

    P Liljeström

  3. Immunopathology Laboratory, Institute for Pathology and Oncology, Karolinska Hospital, Stockholm, Sweden

    P Biberfeld

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  1. P Colmenero
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  2. P Berglund
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  6. M Jondal
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Colmenero, P., Berglund, P., Kambayashi, T. et al. Recombinant Semliki Forest virus vaccine vectors: the route of injection determines the localization of vector RNA and subsequent T cell response. Gene Ther 8, 1307–1314 (2001). https://doi.org/10.1038/sj.gt.3301501

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