Active immunisation targeting soluble murine tumour necrosis factor alpha is safe and effective in collagen-induced arthritis model treatment.

Publisher: Clinical And Experimental Rheumatology S.A.S Country of Publication: Italy NLM ID: 8308521 Publication Model: Print-Electronic Cited Medium: Print ISSN: 0392-856X (Print) Linking ISSN: 0392856X NLM ISO Abbreviation: Clin Exp Rheumatol Subsets: MEDLINE

Publication: Pisa : Clinical And Experimental Rheumatology S.A.S
Original Publication: Pisa, Italy : Pacini editore, [1983-

Vaccination*; Arthritis, Experimental/*therapy ; Tumor Necrosis Factor-alpha/*immunology; Animals ; Antibody Formation ; Arthritis, Experimental/immunology ; Male ; Mice ; Mice, Inbred DBA ; T-Lymphocytes/immunology

Objectives: TNF-α has been proved to be an effective target in rheumatoid arthritis treatment. So far, all the commercialised TNF-α antagonists function as passive immunotherapy. The aim of this study was to design a complex which can trigger active immunisation and overcome self-tolerance to elicit antibodies against murine TNF-α.
Methods: The complex (KLH-TNF) was chemically synthesised by linking a selected peptide TNFα(4-23) from murine soluble TNF-α to a carrier protein, keyhole limpet haemocyanin (KLH). We evaluated its safety and antibody eliciting performance. We also evaluated its disease-regulating ability on collagen-induced arthritis models. Furthermore, the immune cells responses were analysed by T cell proliferation assay and B cell memory experiments.
Results: The complex was safe without cytotoxity. The anti-mTNF-α antibody titers of the KLH-TNF group were 400 times greater than the control groups (p<0.0001). The elicited antibodies could combine with soluble TNF-α. The antibody response was independent of autologous TNF-α and could be reinforced by booster immunisation. Moreover, the complex did not trigger T cell activation and B cell memory response against native TNF-α. In animal experiments, KLH-TNF immunized mice showed a lower arthritis score (p<0.001) and better weight gain (p<0.01). Histological evaluations showed milder inflammation and cartilage depletion.
Conclusions: Active immunotherapy against cytokine TNF-α is feasible by conjugating cytokine peptide with carrier protein. The elicited antibodies could combine with the native TNF-α and inhibit its activity. Importantly, the antibody response is reversible and independent of autologous TNF-α.

0 (Tumor Necrosis Factor-alpha)

Date Created: 20160127 Date Completed: 20160721 Latest Revision: 20170112

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