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Safety of a GM-CSF adjuvant-plasmid DNA malaria vaccine

Gene Therapy volume 8, pages 1011–1023 (2001)Cite this article

Abstract

MuStDO 5 is a multivalent plasmid DNA vaccine for malaria comprised of five plasmid DNAs encoding five proteins from Plasmodium falciparum and one plasmid DNA encoding human GM-CSF. To evaluate the safety of MuStDO 5, a series of pre-clinical studies were conducted in mice and rabbits. In pharmacology studies in mice, GM-CSF could not be detected in the serum following either intramuscular or a combined intramuscular/intradermal administration of the vaccine, but was readily detected in the muscle following intramuscular administration. In a tissue distribution study in mice, MuStDO 5 plasmid DNA was detected by PCR initially in highly vascularized tissues, while at later time-points the plasmid DNA was detected primarily at the site(s) of injection. In GLP safety studies in mice and rabbits, repeated intramuscular/intradermal administration of the MuStDO 5 vaccine was found to be safe and well tolerated without any evidence of autoimmune pathology.

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Acknowledgements

The experiments reported herein were conducted according to the principles set out in the Guide for Care and Use of Laboratory Animals Research, NRC, National Academy Press (1996). This study was supported by Naval Medical Research Center Work Units63002A.810.F.A0011 (STO F), 060379N.01889.135.A0039 (Office of Naval Research Advance Technology Demonstration), 60000.000.000.A0062 (United States Agency for International Development Interagency Agreement) and 0604771N.0933.001.A0065 (Bureau of Medicine and Surgery). The assertions herein are the private ones of the authors and are not to be construed as official or as reflecting the views of the US Navy or the Naval service at large.

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Author notes

  1. SE Parker

    Present address: Lilly Research Laboratories, 2001 W. Main St., P.O. Box 708, Greenfield, 46140, IN, USA

Authors and Affiliations

  1. Vical Inc., San Diego, CA, USA

    SE Parker, H Horton, R Hof, P Hernandez, A Vilalta, J Hartikka, P Hobart & JA Norman

  2. Sierra Biomedical, San Diego, CA, USA

    D Monteith

  3. BioReliance, Inc., Rockville, MD, USA

    D Monteith, CE Bentley & A Chang

  4. Malaria Program, Naval Medical Research Center, Bethesda, MD, USA

    R Hedstrom, WO Rogers, S Kumar & SL Hoffman

  5. Regulatory Affairs, Aventis Pasteur, Inc., Swiftwater, 18370, PA, USA

    R Hedstrom

  6. Celera Genomics, 45 West Gude Drive, Rockville, MD, USA

    SL Hoffman

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Parker, S., Monteith, D., Horton, H. et al. Safety of a GM-CSF adjuvant-plasmid DNA malaria vaccine. Gene Ther 8, 1011–1023 (2001). https://doi.org/10.1038/sj.gt.3301491

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  • DOI: https://doi.org/10.1038/sj.gt.3301491

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