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

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.

• Authors: S E Parker, D Monteith, H Horton, R Hof, P Hernandez, A Vilalta, J Hartikka, P Hobart, C E Bentley, A Chang, R Hedstrom, W O Rogers, S Kumar, S L Hoffman, J A Norman
• Journal: Gene therapy (Gene Ther) Vol. 8 Issue 13 Pg. 1011-23 (Jul 2001) ISSN: 0969-7128 [Print] England
• PMID: 11438836 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Adjuvants, Immunologic
• Antibodies, Antinuclear
• Malaria Vaccines
• Vaccines, DNA
• Granulocyte-Macrophage Colony-Stimulating Factor

Topics

• Adjuvants, Immunologic (pharmacokinetics, toxicity)
• Animals
• Antibodies, Antinuclear (blood)
• Female
• Granulocyte-Macrophage Colony-Stimulating Factor (genetics, pharmacokinetics, toxicity)
• Injections, Intradermal
• Injections, Intramuscular
• Malaria Vaccines (immunology, pharmacokinetics, toxicity)
• Male
• Mice
• Mice, Inbred Strains
• Muscle, Skeletal (metabolism)
• Plasmids
• Polymerase Chain Reaction
• Rabbits
• Tissue Distribution
• Vaccines, DNA (immunology, pharmacokinetics, toxicity)