Zhang and colleagues from Shanghai Jiao Tong University hypothesized that by utilizing a protein currently in use as a vaccine as a scaffold for the TNF peptide, they could reduce the toxicity and increase the stability of the final vaccine.
Zhang et al developed an epitope-scaffold immunogen against TNF-α, in which the conformation of the epitope peptide TNF-α aa 80–97 is stabilized by transplantation onto a scaffold molecule, a transmembrane domain of diphtheria toxin. The researchers assessed the immunogenicity of the vaccine against native TNF-α in mice as well as the therapeutic efficacy in mice with collagen-induced arthritis. The vaccine was administered 2 weeks after inducing disease. The onset of arthritis was delayed by 15 days and its prevalence was halved (~90% versus ~45%) in mice that received the diphtheria toxin–TNF hybrid vaccine, compared with mice that received diphtheria toxin alone. Mice receiving the hybrid TNF vaccine also had an eightfold reduction in their clinical arthritis score, confirmed by histology as a reduction in bone erosion, synovial inflammation, immune cell infiltration and cartilage damage.
The researchers’ results showed that diphtheria toxin-based epitope-scaffold vaccine is a promising strategy for prevention and treatment of autoimmune diseases.
Citation: Zhang, L. et al. A rationally designed TNF-α epitope-scaffold immunogen induces sustained antibody response and alleviates collagen-induced arthritis in mice. PLoS ONE 11,e0163080 (2016).PLOS ONE [/et_pb_text][/et_pb_column][/et_pb_row][/et_pb_section]