Phase I malaria vaccine trial with a long synthetic peptide derived from the merozoite surface protein 3 antigen.
The C-terminal conserved region of Plasmodium falciparum merozoite surface protein 3 (MSP3) is the trigger antigen of a protective immune response mediated by cytophilic antibodies. In an open, randomized, two-adjuvant (Montanide ISA 720, aluminum hydroxide) phase I clinical trial we evaluated the safety and immunogenicity of increasing doses of a long synthetic peptide construct spanning the conserved region of MSP3 targeted by biologically active antibodies (MSP3-LSP). Thirty-five healthy volunteers were randomized to receive three subcutaneous injections on days 0, 30, and 120. Of the 100 injections given, 10 caused severe local reactions, 62 caused transient mild to moderate local reactions, and 28 caused no reaction. On the basis of preestablished exclusion criteria, use of the Montanide formulation led to withdrawal of five volunteers after the second injection. This led to a reduction in the subsequent vaccine doses in four of the groups. No vaccine-related serious adverse events occurred throughout the trial. After the third injection, volunteers displayed a marked specific anti-MSP3-LSP antibody response (23/30 individuals, compared with 29/34 individuals for plasma from an area where malaria is endemic), an anti-native MSP3 antibody response (19/30 individuals), a T-cell-antigen-specific proliferative response (26/30 individuals), and gamma interferon production (25/30 individuals). In conclusion, the MSP3-LSP vaccine was immunogenic with both adjuvants, although it was unacceptably reactogenic when it was combined with Montanide. The potential usefulness of the candidate vaccine is supported by the induction of a strong cytophilic response (i.e., the type of anti-MSP3 antibodies involved in antibody-dependent, monocyte-mediated protective mechanisms in areas where malaria is endemic).
Audran
Régine
R
Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois, BH-19, Rue du Bugnon, 1011 Lausanne, Switzerland.
Cachat
Michel
M
Lurati
Floriana
F
Soe
Soe
S
Leroy
Odile
O
Corradin
Giampietro
G
Druilhe
Pierre
P
Spertini
François
F
D000328:Adult; D000913:Antibodies, Protozoan / Q000097:blood; D000953:Antigens, Protozoan / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D049109:Cell Proliferation; D016207:Cytokines / Q000276:immunology; D005260:Female; D006801:Humans; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D008297:Male; D010446:Peptide Fragments / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D016207:Cytokines; C506685:MSP3 protein, Plasmodium falciparum (181-276); D017780:Malaria Vaccines; D010446:Peptide Fragments; D015800:Protozoan Proteins; D022223:Vaccines, Subunit; C089133:merozoite surface protein 3, Plasmodium