The artificial antimicrobial peptide KLKLLLLLKLK induces predominantly a TH2-type immune response to co-injected antigens

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作   者：

Fritz JH;  Brunner S;  Birnstiel ML;  Buschle M;  Gabain A;  Mattner F;  Zauner W; 

作者机构：

Intercell AG;  1030 Vienna;  Campus Vienna Biocenter 6;  Austria. joerghfritz@hotmail.com; 

关键词：

Immunologic pharmacology;  Immunoglobulin G biosynthesis immunology;  Genes;  Antibodies;  Anti-Infective Agents immunology;  Interleukin-5 biosynthesis;  Immunity;  Interleukin-4 biosynthesis;  Hemagglutination Inhibition Tests;  Flow Cytometry;  Ovalbumin immunology;  Spleen cytology immunology metabolism;  Epitopes immunology;  Antigen-Presenting Cells drug effects immunology;  MHC Class I immunology;  Alum Compounds pharmacology;  Antigens administration & dosage immunology;  Enzyme-Linked Immunosorbent Assay;  Adjuvants;  Cellular physiology;  Inbred C57BL;  Influenza Vaccine immunology;  Animals;  Th2 Cells immunology;  Viral analysis biosynthesis;  Mice;  Oligopeptides pharmacology;  Fluorescent Dyes; 

期刊名称：

Vaccine

i s s n：

0264-410X

年卷期：

2004 年 22 卷 25/26 期

页   码：

3274-3284

页   码：

摘   要：

Cationic antimicrobial peptides (CAMPs) are active defence components of the innate immune system. Several artificial CAMPs have been designed as antibiotic peptide therapeutics, but none have been reported to exert adjuvant activity in animal models. Here we show for the first time that an artificial CAMP, KLKLLLLLKLK (KLKL5KLK), is a potent inducer of adaptive immunity to co-injected antigens in vivo. High levels of antigen-specific antibodies were obtained after co-injection of KLKL5KLK with the model antigen ovalbumin (OVA) or a commercially available influenza vaccine. We show that KLKL5KLK induces a sustained immune response with a prevalent TH2 profile when co-injected with proteinaceous and peptide-based antigens. Furthermore, the immuno-enhancing activity of peptide KLKL5KLK was retained when C-terminally amidated or synthesised as retro-all-D-peptide. We provide evidence that KLKL5KLK enhances the association of antigen to antigen-presenting cells and forms a depot of antigen at the site of injection, making it an interesting adjuvant for novel vaccine design.