Assessment in humans of a synthetic peptide-based vaccine against the sporozoite stage of the human malaria parasite, Plasmodium falciparum.
Eleven volunteers were injected with an anti-malaria (Plasmodium falciparum) sporozoite vaccine candidate consisting of a synthetic peptide, Ac-Cys-(NANP)3, coupled to tetanus toxoid (TT) and adsorbed to aluminum hydroxide. Two of the volunteers had no previously known exposure to TT. Eight volunteers made detectable antipeptide, anticircumsporozoite protein or antisporozoite antibodies, whose titers increased after multiple injections in four individuals. The maximum antisporozoite titer obtained in an immunofluorescence assay was 1280. In those individuals who produced antipeptide antibody, the overall correlation between IgG anti-Ac-Cys-(NANP)3 antibody in enzyme-linked immunosorbent assay and IgG antisporozoite reactivity in immunofluorescence was highly significant. However, the fine specificity of antibody varied among volunteers with two individuals producing mostly antipeptide antibody. Anti-TT antibody responses increased in all volunteers with the exception of that person who had the highest pretrial anti-TT titer; this individual was one of the two pre-TT-immunized volunteers who failed to produce anti-Ac-Cys-(NANP)3 or sporozoite antibody. For the two non-TT preimmunized volunteers, one produced an antisporozoite fluorescence titer of 320; the other made no detectable antibody against either Ac-Cys-(NANP)3 or sporozoites during a primary response. For the three volunteers monitored, after the first injection, significant T cell proliferative responses to (NANP)3 were observed, which increased up to 4 wk after immunization, when a second injection was given. Responsiveness then declined to background levels and did not reappear after further immunizations. In contrast, a marked TT-specific proliferation was observed for the duration of the study.
Etlinger
H M
HM
Central Research Units, F. Hoffmann-La Roche & Co, Ltd, Basel, Switzerland.
Felix
A M
AM
Gillessen
D
D
Heimer
E P
EP
Just
M
M
Pink
J R
JR
Sinigaglia
F
F
Stürchler
D
D
Takacs
B
B
Trzeciak
A
A
D000328:Adult; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D000913:Antibodies, Protozoan / Q000096:biosynthesis; D000918:Antibody Specificity; D000941:Antigens / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008288:Malaria / Q000276:immunology* / Q000469:parasitology; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000276:immunology*; D010963:Plasmodium falciparum / Q000254:growth & development / Q000276:immunology*; D013745:Tetanus Toxoid / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology
D000907:Antibodies, Bacterial; D000913:Antibodies, Protozoan; D000941:Antigens; D009842:Oligopeptides; D013745:Tetanus Toxoid; D014614:Vaccines, Synthetic; C052953:(asparaginyl-alanyl-asparaginyl-proline)3