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.
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.
Kester
Kent E
KE
Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA. kent.kester@na.amedd.army.mil
McKinney
Denise A
DA
Tornieporth
Nadia
N
Ockenhouse
Christian F
CF
Heppner
D Gray
DG
Hall
Ted
T
Wellde
Bruce T
BT
White
Kate
K
Sun
Peifang
P
Schwenk
Robert
R
Krzych
Urszula
U
Delchambre
Martine
M
Voss
Gerald
G
Dubois
Marie-Claude
MC
Gasser
Robert A
RA
Dowler
Megan G
MG
O'Brien
Megan
M
Wittes
Janet
J
Wirtz
Robert
R
Cohen
Joe
J
Ballou
W Ripley
WR
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
D000913:Antibodies, Protozoan; D007074:Immunoglobulin G; D017780:Malaria Vaccines; C493155:RTS,S-AS02A vaccine