title: Safety and immunogenicity of a three-component blood-stage malaria vaccine (MSP1, MSP2, RESA) against Plasmodium falciparum in Papua New Guinean children.
abstract: Combination B is a malaria vaccine that comprises recombinant Plasmodium falciparum (P. falciparum) blood-stage proteins MSP1, MSP2 and RESA, formulated with the adjuvant Montanide ISA 720. A phase I-IIb double-blind randomised placebo-controlled trial was undertaken in 120 children aged 5-9 years. Subjects were randomised in four groups: (i) No sulphadoxine-pyrimethamine (SP)+vaccine, (ii) No SP+placebo, (iii) SP+vaccine, (iv) SP+placebo. 15 microg of each protein were given in the thigh, at both first and second injection (4 weeks apart). The placebo was adjuvant emulsified with saline. No serious or severe AEs occurred. Moderate AEs were seen in 3% of the vaccine and 3% of the placebo recipients after first injection and in 12 and 10% after second injection. The vaccine induced significant antibody responses to all three antigens but triggered an IFN-gamma response to MSP1 only. At Week 12, the IFN-gamma response to MSP1 was substantially higher in the vaccine group where No SP had been given. Combination B proved to be safe and immunogenic in children aged 5-9 years. Vaccine immunogenicity was neither impaired by circulating parasites nor increased after pre-treatment with SP and pre-treatment is not advisable in future trials of malaria vaccines, at least for those including blood-stage antigens.
authors: PNG Institute of Medical Research, Maprik, Papua, New Guinea. blaise.genton@hospvd.ch
authors: Blaise
authors: B
authors: Genton
authors: Fadwa
authors: F
authors: Al-Yaman
authors: Inoni
authors: I
authors: Betuela
authors: Robin F
authors: RF
authors: Anders
authors: Allan
authors: A
authors: Saul
authors: Kay
authors: K
authors: Baea
authors: Mata
authors: M
authors: Mellombo
authors: Jack
authors: J
authors: Taraika
authors: Graham V
authors: GV
authors: Brown
authors: David
authors: D
authors: Pye
authors: David O
authors: DO
authors: Irving
authors: Ingrid
authors: I
authors: Felger
authors: Hans-Peter
authors: HP
authors: Beck
authors: Thomas A
authors: TA
authors: Smith
authors: Michael P
authors: MP
authors: Alpers
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000032:analysis / Q000096:biosynthesis; D002455:Cell Division; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D016207:Cytokines / Q000032:analysis / Q000096:biosynthesis; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007114:Immunization; D007074:Immunoglobulin G / Q000032:analysis / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000032:analysis / Q000096:biosynthesis; D015847:Interleukin-4 / Q000032:analysis / Q000096:biosynthesis; D017780:Malaria Vaccines / Q000009:adverse effects / Q000276:immunology*; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000276:immunology* / Q000517:prevention & control*; D009000:Monocytes / Q000276:immunology; D010219:Papua New Guinea / Q000453:epidemiology; D010963:Plasmodium falciparum / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000096:biosynthesis
chemical_list: D000913:Antibodies, Protozoan; D016207:Cytokines; D007074:Immunoglobulin G; D017780:Malaria Vaccines; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma