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Infection and Immunity, December 2005, p. 8017-8026, Vol. 73, No. 12
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.12.8017-8026.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Phase I Malaria Vaccine Trial with a Long Synthetic Peptide Derived from the Merozoite Surface Protein 3 Antigen

Régine Audran,1,2 Michel Cachat,1 Floriana Lurati,1 Soe Soe,3 Odile Leroy,4 Giampietro Corradin,2 Pierre Druilhe,3 and François Spertini1*

Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland,1 Institute of Biochemistry, University of Lausanne, Epalinges, Switzerland,2 Biomedical Parasitology Unit, Pasteur Institute, Paris, France,3 European Malaria Vaccine Initiative, Center of International Health, Bergen University, Bergen, Norway4

Received 9 June 2004/ Returned for modification 15 August 2004/ Accepted 17 August 2005

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).

* Corresponding author. Mailing address: Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois, BH-19, Rue du Bugnon, 1011 Lausanne, Switzerland. Phone: 41 21 314 0790. Fax: 41 21 314 0791. E-mail: francois.spertini{at}chuv.ch.

Editor: J. F. Urban, Jr.

Infection and Immunity, December 2005, p. 8017-8026, Vol. 73, No. 12
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.12.8017-8026.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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