A virosomal malaria peptide vaccine elicits a long-lasting sporozoite-inhibitory antibody response in a phase 1a clinical trial.

Détails

ID Serval
serval:BIB_42759A602BF6
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
A virosomal malaria peptide vaccine elicits a long-lasting sporozoite-inhibitory antibody response in a phase 1a clinical trial.
Périodique
Plos One
Auteur(s)
Okitsu S.L., Silvie O., Westerfeld N., Curcic M., Kammer A.R., Mueller M.S., Sauerwein R.W., Robinson J.A., Genton B., Mazier D., Zurbriggen R., Pluschke G.
ISSN
1932-6203[electronic]
Statut éditorial
Publié
Date de publication
2007
Volume
2
Numéro
12
Pages
e1278
Langue
anglais
Résumé
OBJECTIVES: Peptides delivered on the surface of influenza virosomes have been shown to induce solid humoral immune responses in experimental animals. High titers of peptide-specific antibodies were also induced in a phase 1a clinical trial in volunteers immunized with virosomal formulations of two peptides derived from the circumsporozoite protein (CSP) and the apical membrane antigen 1 (AMA-1) of Plasmodium falciparum. The main objective of this study was to perform a detailed immunological and functional analysis of the CSP-specific antibodies elicited in this phase 1a trial.
METHODOLOGY/PRINCIPAL FINDINGS: 46 healthy malaria-naïve adults were immunized with virosomal formulations of two peptide-phosphatidylethanolamine conjugates, one derived from the NANP repeat region of P. falciparum CSP (designated UK-39) the other from P. falciparum AMA-1 (designated AMA49-C1). The two antigens were delivered in two different concentrations, alone and in combination. One group was immunized with empty virosomes as control. In this report we show a detailed analysis of the antibody response against UK-39. Three vaccinations with a 10 microg dose of UK-39 induced high titers of sporozoite-binding antibodies in all volunteers. This IgG response was affinity maturated and long-lived. Co-administration of UK-39 and AMA49-C1 loaded virosomes did not interfere with the immunogenicity of UK-39. Purified total IgG from UK-39 immunized volunteers inhibited sporozoite migration and invasion of hepatocytes in vitro. Sporozoite inhibition closely correlated with titers measured in immunogenicity assays.
CONCLUSIONS: Virosomal delivery of a short, conformationally constrained peptide derived from P. falciparum CSP induced a long-lived parasite-inhibitory antibody response in humans. Combination with a second virosomally-formulated peptide derived from P. falciparum AMA-1 did not interfere with the immunogenicity of either peptide, demonstrating the potential of influenza virosomes as a versatile, human-compatible antigen delivery platform for the development of multivalent subunit vaccines.
TRIAL REGISTRATION: ClinicalTrials.gov NCT00400101.
Mots-clé
Adult, Animals, Antibodies, Protozoan/biosynthesis, Blotting, Western, Cross Reactions, Electrophoresis, Polyacrylamide Gel, Enzyme-Linked Immunosorbent Assay, Fluorescent Antibody Technique, Indirect, Humans, Malaria Vaccines/immunology, Plasmodium falciparum/immunology, Virosomes/immunology
Pubmed
Open Access
Oui
Création de la notice
03/07/2010 9:25
Dernière modification de la notice
20/08/2019 14:45
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