Titre
Phase I malaria vaccine trial with a long synthetic peptide derived from the merozoite surface protein 3 antigen
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Audran, R.
Auteure/Auteur
Cachat, M.
Auteure/Auteur
Lurati, F.
Auteure/Auteur
Soe, S.
Auteure/Auteur
Leroy, O.
Auteure/Auteur
Corradin, G.
Auteure/Auteur
Druilhe, P.
Auteure/Auteur
Spertini, F.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
0019-9567
Statut éditorial
Publié
Date de publication
2005-12
Volume
73
Numéro
12
Première page
8017
Dernière page/numéro d’article
26
Peer-reviewed
Oui
Langue
anglais
Notes
Clinical Trial, Phase I
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't --- Old month value: Dec
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't --- Old month value: Dec
Résumé
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).
Sujets
PID Serval
serval:BIB_FE3CF85509B0
PMID
Open Access
Oui
Date de création
2008-01-24T13:55:25.406Z
Date de création dans IRIS
2025-05-21T06:07:48Z
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Nom
Audran R IAI 2005.pdf
Version du manuscrit
published
Taille
287.22 KB
Format
Adobe PDF
PID Serval
serval:BIB_FE3CF85509B0.P001
URN
urn:nbn:ch:serval-BIB_FE3CF85509B05
Somme de contrôle
(MD5):03f1b8be8342415286ecc22d4b279b6f