title: A phase I/IIa safety, immunogenicity, and efficacy bridging randomized study of a two-dose regimen of liquid and lyophilized formulations of the candidate malaria vaccine RTS,S/AS02A in malaria-naïve adults.
abstract: We conducted an open-label safety and immunogenicity bridging study that compared liquid and lyophilized formulations of the candidate malaria vaccine RTS,S formulated in AS02A in 34 healthy, malaria-naïve adults at WRAIR. Volunteers received two doses of either formulation on a 0, 1-month schedule. Both vaccines were well tolerated and similarly immunogenic. Nineteen of 25 subjects who received the lyophilized formulation and six infectivity controls underwent sporozoite challenge to assess vaccine efficacy. All six controls had parasitemia detectable by thick blood smear by day 13 (mean pre-patent period 12.3 days; range 11-13). In the vaccine group, 8 of 19 vaccinees did not develop malaria and were completely protected (i.e., 42%). Among the 11 vaccinees who did become infected, the mean pre-patent period was delayed (14.4 days; range 13-18). The two formulations of RTS,S were equally safe and immunogenic, and the lyophilized formulation showed similar levels of efficacy against sporozoite challenge to that conferred by the liquid formulation in previous studies.
authors.affiliation: Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA. kent.kester@na.amedd.army.mil
authors.forename: Kent E
authors.initials: KE
authors.lastname: Kester
authors.forename: Denise A
authors.initials: DA
authors.lastname: McKinney
authors.forename: Nadia
authors.initials: N
authors.lastname: Tornieporth
authors.forename: Christian F
authors.initials: CF
authors.lastname: Ockenhouse
authors.forename: D Gray
authors.initials: DG
authors.lastname: Heppner
authors.forename: Ted
authors.initials: T
authors.lastname: Hall
authors.forename: Bruce T
authors.initials: BT
authors.lastname: Wellde
authors.forename: Kate
authors.initials: K
authors.lastname: White
authors.forename: Peifang
authors.initials: P
authors.lastname: Sun
authors.forename: Robert
authors.initials: R
authors.lastname: Schwenk
authors.forename: Urszula
authors.initials: U
authors.lastname: Krzych
authors.forename: Martine
authors.initials: M
authors.lastname: Delchambre
authors.forename: Gerald
authors.initials: G
authors.lastname: Voss
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Dubois
authors.forename: Robert A
authors.initials: RA
authors.lastname: Gasser
authors.forename: Megan G
authors.initials: MG
authors.lastname: Dowler
authors.forename: Megan
authors.initials: M
authors.lastname: O'Brien
authors.forename: Janet
authors.initials: J
authors.lastname: Wittes
authors.forename: Robert
authors.initials: R
authors.lastname: Wirtz
authors.forename: Joe
authors.initials: J
authors.lastname: Cohen
authors.forename: W Ripley
authors.initials: WR
authors.lastname: Ballou
mesh_terms: D000293:Adolescent; D000328:Adult; D000913:Antibodies, Protozoan / Q000097:blood; D049109:Cell Proliferation; D002478:Cells, Cultured; D002626:Chemistry, Pharmaceutical; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005612:Freeze Drying; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008288:Malaria / Q000276:immunology / Q000517:prevention & control*; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D018512:Parasitemia
chemical_list: D000913:Antibodies, Protozoan; D007074:Immunoglobulin G; D017780:Malaria Vaccines; C493155:RTS,S-AS02A vaccine