Characterization of a multi-lipopeptides mixture used as an HIV-1 vaccine candidate.
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.
Klinguer
C
C
UMR 8525, IBL, Institut Pasteur de Lille, 1 rue Calmette, 59021, Lille, France.
David
D
D
Kouach
M
M
Wieruszeski
J M
JM
Tartar
A
A
Marzin
D
D
Levy
J P
JP
Gras-Masse
H
H
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
D016915:AIDS Vaccines; D008074:Lipoproteins; D010455:Peptides