title: Human phase I vaccine trials of 3 recombinant asexual stage malaria antigens with Montanide ISA720 adjuvant.
abstract: Two phase I vaccine trials were conducted to test the immunogenicity and safety of a vaccine containing three recombinant malaria antigens from the asexual stage of Plasmodium falciparum. The three antigens are a fragment of MSP1 (190LCS.T3); MSP2 and a portion of RESA and were formulated in Montanide ISA720 adjuvant. These trials investigated the dose response of each antigen for eliciting both antibody and T-cell responses and the immunogenicity of a mixture of the antigens compared with the antigens injected separately. All three antigens elicited both antibody and T-cell responses. Strong T-cell responses were observed with 190LCS.T3 and RESA with stimulation indices exceeding 100 for peripheral blood leucocytes in some individuals. The antibody responses were generally weak. The human antibody responses observed with MSP2 in Montanide ISA720 were not significantly different from those obtained in an earlier trial which used MSP2 with alum as the adjuvant. No antigenic competition was observed: volunteers receiving a mixture of antigens had similar responses to those receiving the three antigens at separate sites. Tenderness and pain at the injection site were common over the first few days following immunization. In some volunteers, especially those receiving the highest doses tested, there was a delayed reaction at the injection site with pain and swelling occurring approximately 10 days after injection.
authors.affiliation: CRC for Vaccine Technology and Australian Centre for International and Tropical Health and Nutrition, The Queensland Institute of Medical Research, Royal Brisbane Hospital, Australia. allans@qimr.edu.au
authors.forename: A
authors.initials: A
authors.lastname: Saul
authors.forename: G
authors.initials: G
authors.lastname: Lawrence
authors.forename: A
authors.initials: A
authors.lastname: Smillie
authors.forename: C M
authors.initials: CM
authors.lastname: Rzepczyk
authors.forename: C
authors.initials: C
authors.lastname: Reed
authors.forename: D
authors.initials: D
authors.lastname: Taylor
authors.forename: K
authors.initials: K
authors.lastname: Anderson
authors.forename: A
authors.initials: A
authors.lastname: Stowers
authors.forename: R
authors.initials: R
authors.lastname: Kemp
authors.forename: A
authors.initials: A
authors.lastname: Allworth
authors.forename: R F
authors.initials: RF
authors.lastname: Anders
authors.forename: G V
authors.initials: GV
authors.lastname: Brown
authors.forename: D
authors.initials: D
authors.lastname: Pye
authors.forename: P
authors.initials: P
authors.lastname: Schoofs
authors.forename: D O
authors.initials: DO
authors.lastname: Irving
authors.forename: S L
authors.initials: SL
authors.lastname: Dyer
authors.forename: G C
authors.initials: GC
authors.lastname: Woodrow
authors.forename: W R
authors.initials: WR
authors.lastname: Briggs
authors.forename: R
authors.initials: R
authors.lastname: Reber
authors.forename: D
authors.initials: D
authors.lastname: Stürchler
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000328:Adult; D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis; D000953:Antigens, Protozoan / Q000276:immunology*; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D007117:Immunization, Secondary; D008213:Lymphocyte Activation / Q000276:immunology; D017780:Malaria Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology / Q000633:toxicity; D016778:Malaria, Falciparum / Q000276:immunology / Q000517:prevention & control; D008297:Male; D008353:Mannitol / Q000008:administration & dosage / Q000031:analogs & derivatives*; D051379:Mice; D008807:Mice, Inbred BALB C; D009829:Oleic Acids / Q000008:administration & dosage*; D015800:Protozoan Proteins / Q000276:immunology; D016037:Single-Blind Method; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D017780:Malaria Vaccines; D009829:Oleic Acids; D015800:Protozoan Proteins; C065974:merozoite surface protein 2, Plasmodium; C001681:mannide monooleate; D008353:Mannitol