Phase 1 randomized double-blind safety and immunogenicity trial of Plasmodium falciparum malaria merozoite surface protein FMP1 vaccine, adjuvanted with AS02A, in adults in western Kenya.
We report the first trial of candidate malaria vaccine antigen FMP1, a 42kDa fragment from the C-terminus of merozoite surface protein-1 (MSP-1) from the 3D7 strain of Plasmodium falciparum, in an endemic area. Forty adult male and female residents of western Kenya were enrolled to receive 3 doses of either FMP1/AS02A or Imovax rabies vaccine by intra-deltoid injection on a 0, 1, 2 month schedule. Thirty-seven volunteers received all three immunizations and 38 completed the 12-month evaluation period. Slightly more recipients of the FMP1/AS02A vaccine experienced any instance of pain at 24 h post-immunization than in the Imovax group (95% versus 65%), but otherwise the two vaccines were equally safe and well-tolerated. Baseline antibody levels were high in both groups and were boosted in the FMP1/AS02A group. Longitudinal models revealed a highly significant difference between groups for both the average post-baseline antibody responses to MSP-1(42) (F1,335=13.16; P<0.001) and the Day 90 responses to MSP-1(42) (F1,335=16.69; P<0.001). The FMP1/AS02A vaccine is safe and immunogenic in adults and should progress to safety testing in children at greatest risk of malaria.
Stoute
José A
JA
US Army Medical Research Unit and the Kenya Medical Research Institute, Nairobi, Kenya. jstoute@usuhs.mil
Gombe
Joash
J
Withers
Mark R
MR
Siangla
Joram
J
McKinney
Denise
D
Onyango
Melanie
M
Cummings
James F
JF
Milman
Jessica
J
Tucker
Kathryn
K
Soisson
Lorraine
L
Stewart
V Ann
VA
Lyon
Jeffrey A
JA
Angov
Evelina
E
Leach
Amanda
A
Cohen
Joe
J
Kester
Kent E
KE
Ockenhouse
Christian F
CF
Holland
Carolyn A
CA
Diggs
Carter L
CL
Wittes
Janet
J
Heppner
D Gray
DG
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000009:adverse effects; D000328:Adult; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D006801:Humans; D007630:Kenya; D008050:Lipid A / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000276:immunology; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D016778:Malaria, Falciparum / Q000276:immunology / Q000469:parasitology / Q000517:prevention & control*; D008297:Male; D020066:Merozoite Surface Protein 1 / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D008875:Middle Aged; D010963:Plasmodium falciparum / Q000276:immunology; D012503:Saponins / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D016896:Treatment Outcome
C501939:ASO2A adjuvant; D000276:Adjuvants, Immunologic; D000913:Antibodies, Protozoan; D004338:Drug Combinations; D008050:Lipid A; D017780:Malaria Vaccines; D020066:Merozoite Surface Protein 1; D012503:Saponins