The artificial antimicrobial peptide KLKLLLLLKLK induces predominantly a TH2-type immune response to co-injected antigens.
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.
Fritz
Jörg H
JH
Intercell AG, Campus Vienna Biocenter 6, 1030 Vienna, Austria. joerghfritz@hotmail.com
Brunner
Sylvia
S
Birnstiel
Max L
ML
Buschle
Michael
M
Gabain
Alexander v
Av
Mattner
Frank
F
Zauner
Wolfgang
W
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000534:Alum Compounds / Q000494:pharmacology; D000818:Animals; D000890:Anti-Infective Agents / Q000276:immunology*; D000914:Antibodies, Viral / Q000032:analysis / Q000096:biosynthesis; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology; D000941:Antigens / Q000008:administration & dosage / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology; D005434:Flow Cytometry; D005456:Fluorescent Dyes; D005805:Genes, MHC Class I / Q000276:immunology; D006385:Hemagglutination Inhibition Tests; D007111:Immunity, Cellular / Q000502:physiology*; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology; D007252:Influenza Vaccines / Q000276:immunology; D015847:Interleukin-4 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D009842:Oligopeptides / Q000494:pharmacology*; D010047:Ovalbumin / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D000890:Anti-Infective Agents; D000914:Antibodies, Viral; D000941:Antigens; D000939:Epitopes; D005456:Fluorescent Dyes; D007074:Immunoglobulin G; D007252:Influenza Vaccines; D015848:Interleukin-5; D009842:Oligopeptides; C096884:nysyl-leucyl-lysyl-leucyl-leucyl-leucyl-leucyl-leucyl-lysyl-leucyl-lysinamide; D015847:Interleukin-4; C041524:aluminum sulfate; D010047:Ovalbumin