title: Phase I trial of two recombinant vaccines containing the 19kd carboxy terminal fragment of Plasmodium falciparum merozoite surface protein 1 (msp-1(19)) and T helper epitopes of tetanus toxoid.
abstract: The safety and immunogenicity of 2 yeast-derived, blood-stage malaria vaccines were evaluated in a phase l trial. Healthy adults were given 2 or 3 doses of alum-adsorbed vaccine containing the 19 kDa carboxy-terminal fragment of the merozoite surface protein-1 (MSP-1(19)) derived from the 3D7 or the FVO strain of Plasmodium falciparum fused to tetanus toxoid T-helper epitopes P30 and P2. The first 2 doses of MSP-1(19) were well tolerated. Hypersensitivity reactions occurred in 3 subjects after the third dose of MSP-1(19), including bilateral injection site reactions in 2 (one with generalized skin rash), and probable histamine-associated hypotension in 1. Serum antibody responses to MSP-1(19) occurred in 5/16, 9/16 and 0/8 subjects given 20 microg of MSP-1(19), 200 microg of MSP-1(19), and control vaccines (hepatitis B or Td), respectively. Both MSP-1(19) vaccines were immunogenic in humans, but changes in formulation will be necessary to improve safety and immunogenicity profiles.
authors.affiliation: Department of Microbiology & Immunology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA. wkeitel@bcm.tmc.edu
authors.forename: W A
authors.initials: WA
authors.lastname: Keitel
authors.forename: K E
authors.initials: KE
authors.lastname: Kester
authors.forename: R L
authors.initials: RL
authors.lastname: Atmar
authors.forename: A C
authors.initials: AC
authors.lastname: White
authors.forename: N H
authors.initials: NH
authors.lastname: Bond
authors.forename: C A
authors.initials: CA
authors.lastname: Holland
authors.forename: U
authors.initials: U
authors.lastname: Krzych
authors.forename: D R
authors.initials: DR
authors.lastname: Palmer
authors.forename: A
authors.initials: A
authors.lastname: Egan
authors.forename: C
authors.initials: C
authors.lastname: Diggs
authors.forename: W R
authors.initials: WR
authors.lastname: Ballou
authors.forename: B F
authors.initials: BF
authors.lastname: Hall
authors.forename: D
authors.initials: D
authors.lastname: Kaslow
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D018984:Epitopes, T-Lymphocyte; D006801:Humans; D008213:Lymphocyte Activation; D017780:Malaria Vaccines / Q000009:adverse effects / Q000276:immunology*; D020066:Merozoite Surface Protein 1 / Q000276:immunology*; D008875:Middle Aged; D010446:Peptide Fragments / Q000276:immunology*; D010963:Plasmodium falciparum / Q000276:immunology*; D012882:Skin Tests; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D013745:Tetanus Toxoid / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology*
chemical_list: D000913:Antibodies, Protozoan; D018984:Epitopes, T-Lymphocyte; D017780:Malaria Vaccines; D020066:Merozoite Surface Protein 1; D010446:Peptide Fragments; D013745:Tetanus Toxoid; D014614:Vaccines, Synthetic