title: Characterization of a multi-lipopeptides mixture used as an HIV-1 vaccine candidate.
abstract: A multi-component vaccine has been defined, which contains six different synthetic 24- to 32-amino acid lipopeptides derived from the sequence of HIV-1 proteins. The physicochemical properties of the lipopeptide components were compatible with multi-dimensional analysis, using RP-HPLC, Edman sequencing, electrospray mass spectrometry, and 2D-NMR. Detailed analysis of the impurity profiles led to the detection and evaluation of the relative proportions of most by-products: several contaminants resulted from the formation of acetylated fragments, transpeptidation reactions with succinimide or piperidide formation, or methionine and/or tryptophan mono-oxidations. The first batch to be produced underwent extensive pharmacotoxicological testings to confirm its safety; this vaccine candidate has now been used in phase I clinical trials. Despite the complexity of such multi-lipopeptide vaccines, our findings suggest the possibility of preparing a clear and precise assignment of by-products to toxicologically qualified impurities in the eventuality of a future production of several successive batches.
authors.affiliation: UMR 8525, IBL, Institut Pasteur de Lille, 1 rue Calmette, 59021, Lille, France.
authors.forename: C
authors.initials: C
authors.lastname: Klinguer
authors.forename: D
authors.initials: D
authors.lastname: David
authors.forename: M
authors.initials: M
authors.lastname: Kouach
authors.forename: J M
authors.initials: JM
authors.lastname: Wieruszeski
authors.forename: A
authors.initials: A
authors.lastname: Tartar
authors.forename: D
authors.initials: D
authors.lastname: Marzin
authors.forename: J P
authors.initials: JP
authors.lastname: Levy
authors.forename: H
authors.initials: H
authors.lastname: Gras-Masse
mesh_terms: D016915:AIDS Vaccines / Q000009:adverse effects*; D000595:Amino Acid Sequence; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004306:Dose-Response Relationship, Immunologic; D004353:Drug Evaluation, Preclinical; D005260:Female; D015497:HIV-1 / Q000276:immunology*; D008074:Lipoproteins / Q000138:chemical synthesis / Q000276:immunology*; D008297:Male; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology*; D011817:Rabbits
chemical_list: D016915:AIDS Vaccines; D008074:Lipoproteins; D010455:Peptides