title: Safety, tolerability and humoral immune responses after intramuscular administration of a malaria DNA vaccine to healthy adult volunteers.
abstract: DNA-based vaccines are considered to be potentially revolutionary due to their ease of production, low cost, long shelf life, lack of requirement for a cold chain and ability to induce good T-cell responses. Twenty healthy adult volunteers were enrolled in a Phase I safety and tolerability clinical study of a DNA vaccine encoding a malaria antigen. Volunteers received 3 intramuscular injections of one of four different dosages (20, 100, 500 and 2500 microg) of the Plasmodium falciparum circumsporozoite protein (PfCSP) plasmid DNA at monthly intervals and were followed for up to twelve months. Local reactogenicity and systemic symptoms were few and mild. There were no severe or serious adverse events, clinically significant biochemical or hematologic changes, or detectable anti-dsDNA antibodies. Despite induction of excellent CTL responses, intramuscular DNA vaccination via needle injection failed to induce detectable antigen-specific antibodies in any of the volunteers.
authors.affiliation: US Army Medical Research Institute of Infectious Diseases, Ft. Detrick, MD, USA.
authors.forename: T P
authors.initials: TP
authors.lastname: Le
authors.forename: K M
authors.initials: KM
authors.lastname: Coonan
authors.forename: R C
authors.initials: RC
authors.lastname: Hedstrom
authors.forename: Y
authors.initials: Y
authors.lastname: Charoenvit
authors.forename: M
authors.initials: M
authors.lastname: Sedegah
authors.forename: J E
authors.initials: JE
authors.lastname: Epstein
authors.forename: S
authors.initials: S
authors.lastname: Kumar
authors.forename: R
authors.initials: R
authors.lastname: Wang
authors.forename: D L
authors.initials: DL
authors.lastname: Doolan
authors.forename: J D
authors.initials: JD
authors.lastname: Maguire
authors.forename: S E
authors.initials: SE
authors.lastname: Parker
authors.forename: P
authors.initials: P
authors.lastname: Hobart
authors.forename: J
authors.initials: J
authors.lastname: Norman
authors.forename: S L
authors.initials: SL
authors.lastname: Hoffman
mesh_terms: D000328:Adult; D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D017780:Malaria Vaccines / Q000009:adverse effects / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010865:Pilot Projects; D010963:Plasmodium falciparum / Q000276:immunology; D011247:Pregnancy; D015800:Protozoan Proteins / Q000276:immunology; D019444:Vaccines, DNA / Q000009:adverse effects / Q000276:immunology*
chemical_list: D000913:Antibodies, Protozoan; D017780:Malaria Vaccines; D015800:Protozoan Proteins; D019444:Vaccines, DNA; C041595:circumsporozoite protein, Protozoan