Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

Monoclonal antibodies (mAbs) inhibiting cytokines have recently emerged as new drug modalities for the treatment of chronic inflammatory diseases. Interleukin-17 (IL-17) is a T-cell-derived central mediator of autoimmunity. Immunization with Qβ-IL-17, a virus-like particle based vaccine, has been shown to produce autoantibodies in mice and was effective in ameliorating disease symptoms in animal models of autoimmunity. To characterize autoantibodies induced by vaccination at the molecular level, we generated mouse mAbs specific for IL-17 and compared them to germline Ig sequences. The variable regions of a selected hypermutated high-affinity anti-IL-17 antibody differed in only three amino acid residues compared to the likely germline progenitor. An antibody, which was backmutated to germline, maintained a surprisingly high affinity (0.5 nM). The ability of the parental hypermutated antibody and the derived germline antibody to block inflammation was subsequently tested in murine models of multiple sclerosis (experimental autoimmune encephalomyelitis), arthritis (collagen-induced arthritis), and psoriasis (imiquimod-induced skin inflammation). Both antibodies were able to delay disease onset and significantly reduced disease severity. Thus, the mouse genome unexpectedly encodes for antibodies with the ability to functionally neutralize IL-17 in vivo.

Original publication

DOI

10.1002/eji.201445017

Type

Journal article

Journal

Eur J Immunol

Publication Date

04/2015

Volume

45

Pages

1238 - 1247

Keywords

Affinity, Antibody, Collagen-induced arthritis, Experimental autoimmune encephalitis, IL-17 Psoriasis, Animals, Antibodies, Monoclonal, Antibodies, Neutralizing, Arthritis, Experimental, Autoantibodies, Autoimmune Diseases, Base Sequence, Disease Models, Animal, Encephalomyelitis, Autoimmune, Experimental, Female, Hybridomas, Immunoglobulin G, Immunoglobulin Variable Region, Immunotherapy, Inflammation, Interleukin-17, Male, Mice, Mice, Inbred C57BL, Mice, Inbred DBA, Molecular Sequence Data, Psoriasis, Sequence Alignment, Single-Chain Antibodies, Vaccination, Vaccines, Conjugate