title: Safety, tolerability, and lack of antibody responses after administration of a PfCSP DNA malaria vaccine via needle or needle-free jet injection, and comparison of intramuscular and combination intramuscular/intradermal routes.
abstract: Introduction of a new vaccine requires choosing a delivery system that provides safe administration and the desired level of immunogenicity. The safety, tolerability, and immunogenicity of three monthly 2.5-mg doses of a PfCSP DNA vaccine were evaluated in healthy volunteers as administered intramuscularly (IM) by needle, IM by jet injection (Biojector or IM/intradermally (ID) by jet injection. Vaccine administration was well-tolerated. Adverse events were primarily mild and limited to the site of injection (98%). Jet injections (either IM or ID) were associated with approximately twice as many adverse events per immunization as needle IM, but nevertheless were strongly and consistently preferred in opinion polls taken during the study. No volunteers had clinically significant biochemical or hematologic changes or detectable anti-dsDNA antibodies. In conclusion, the injection of Plasmodium falciparum circumsporozoite (PfCSP) DNA vaccine appeared to be safe and well-tolerated when administered by any of the three modes of delivery. However, despite improved antibody responses following both jet injection and ID delivery in animal models, no antibodies could be detected in volunteers by immunofluorescence antibody test (IFAT) or enzyme-linked immunosorbent assay (ELISA) after DNA vaccination.
authors.affiliation: Malaria Program, Naval Medical Research Center, Silver Spring, MD 20910, USA. epsteinj@nmrc.navy.mil
authors.forename: Judith E
authors.initials: JE
authors.lastname: Epstein
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Gorak
authors.forename: Yupin
authors.initials: Y
authors.lastname: Charoenvit
authors.forename: Ruobing
authors.initials: R
authors.lastname: Wang
authors.forename: Nicole
authors.initials: N
authors.lastname: Freydberg
authors.forename: Oluwatoyin
authors.initials: O
authors.lastname: Osinowo
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Richie
authors.forename: Erin L
authors.initials: EL
authors.lastname: Stoltz
authors.forename: Fernando
authors.initials: F
authors.lastname: Trespalacios
authors.forename: John
authors.initials: J
authors.lastname: Nerges
authors.forename: Jennifer
authors.initials: J
authors.lastname: Ng
authors.forename: Victoria
authors.initials: V
authors.lastname: Fallarme-Majam
authors.forename: Esteban
authors.initials: E
authors.lastname: Abot
authors.forename: Lucy
authors.initials: L
authors.lastname: Goh
authors.forename: Suezanne
authors.initials: S
authors.lastname: Parker
authors.forename: Sanjai
authors.initials: S
authors.lastname: Kumar
authors.forename: Richard C
authors.initials: RC
authors.lastname: Hedstrom
authors.forename: Jon
authors.initials: J
authors.lastname: Norman
authors.forename: Richard
authors.initials: R
authors.lastname: Stout
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Hoffman
mesh_terms: D000818:Animals; D006801:Humans; D007271:Injections, Intradermal; D007273:Injections, Intramuscular; D008288:Malaria / Q000276:immunology / Q000517:prevention & control*; D010963:Plasmodium falciparum / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology
chemical_list: D019444:Vaccines, DNA