Protective effect of a germline, IL-17-neutralizing antibody in murine models of autoimmune inflammatory disease.

Dallenbach, Kiran; Maurer, Patrik; Röhn, Till; Zabel, Franziska; Kopf, Manfred; Bachmann, Martin (2015). Protective effect of a germline, IL-17-neutralizing antibody in murine models of autoimmune inflammatory disease. European journal of immunology, 45(4), pp. 1238-1247. Wiley-VCH 10.1002/eji.201445017

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Rheumatology and Immunology

UniBE Contributor:

Bachmann, Martin (B)

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0014-2980

Publisher:

Wiley-VCH

Language:

English

Submitter:

Stefan Kuchen

Date Deposited:

13 Apr 2016 11:08

Last Modified:

29 Mar 2023 23:34

Publisher DOI:

10.1002/eji.201445017

PubMed ID:

25545966

Uncontrolled Keywords:

Affinity, Antibody, Collagen-induced arthritis, Experimental autoimmune encephalitis, IL-17 Psoriasis

BORIS DOI:

10.7892/boris.80939

URI:

https://boris.unibe.ch/id/eprint/80939

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