title: 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: Vical Inc., San Diego, CA 92121, USA.
authors: S E
authors: SE
authors: Parker
authors: D
authors: D
authors: Monteith
authors: H
authors: H
authors: Horton
authors: R
authors: R
authors: Hof
authors: P
authors: P
authors: Hernandez
authors: A
authors: A
authors: Vilalta
authors: J
authors: J
authors: Hartikka
authors: P
authors: P
authors: Hobart
authors: C E
authors: CE
authors: Bentley
authors: A
authors: A
authors: Chang
authors: R
authors: R
authors: Hedstrom
authors: W O
authors: WO
authors: Rogers
authors: S
authors: S
authors: Kumar
authors: S L
authors: SL
authors: Hoffman
authors: J A
authors: JA
authors: Norman
mesh_terms: D000276:Adjuvants, Immunologic / Q000493:pharmacokinetics / Q000633:toxicity*; D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000493:pharmacokinetics / Q000633:toxicity*; D007271:Injections, Intradermal; D007273:Injections, Intramuscular; D017780:Malaria Vaccines / Q000276:immunology / Q000493:pharmacokinetics / Q000633:toxicity*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018482:Muscle, Skeletal / Q000378:metabolism; D010957:Plasmids; D016133:Polymerase Chain Reaction; D011817:Rabbits; D014018:Tissue Distribution; D019444:Vaccines, DNA / Q000276:immunology / Q000493:pharmacokinetics / Q000633:toxicity*
chemical_list: D000276:Adjuvants, Immunologic; D000974:Antibodies, Antinuclear; D017780:Malaria Vaccines; D019444:Vaccines, DNA; D016178:Granulocyte-Macrophage Colony-Stimulating Factor