Safety of a GM-CSF adjuvant-plasmid DNA malaria vaccine.
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.
Parker
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SE
Vical Inc., San Diego, CA 92121, USA.
Monteith
D
D
Horton
H
H
Hof
R
R
Hernandez
P
P
Vilalta
A
A
Hartikka
J
J
Hobart
P
P
Bentley
C E
CE
Chang
A
A
Hedstrom
R
R
Rogers
W O
WO
Kumar
S
S
Hoffman
S L
SL
Norman
J A
JA
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*
D000276:Adjuvants, Immunologic; D000974:Antibodies, Antinuclear; D017780:Malaria Vaccines; D019444:Vaccines, DNA; D016178:Granulocyte-Macrophage Colony-Stimulating Factor