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.
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.
Keitel
W A
WA
Department of Microbiology & Immunology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA. wkeitel@bcm.tmc.edu
Kester
K E
KE
Atmar
R L
RL
White
A C
AC
Bond
N H
NH
Holland
C A
CA
Krzych
U
U
Palmer
D R
DR
Egan
A
A
Diggs
C
C
Ballou
W R
WR
Hall
B F
BF
Kaslow
D
D
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*
D000913:Antibodies, Protozoan; D018984:Epitopes, T-Lymphocyte; D017780:Malaria Vaccines; D020066:Merozoite Surface Protein 1; D010446:Peptide Fragments; D013745:Tetanus Toxoid; D014614:Vaccines, Synthetic