Complex TNF-α B cell epitope MAP vaccine alleviates murine ulcerative colitis

Abstract

The present study aimed to develop a tumor necrosis factor-α (TNF-α) B-cell epitope/IL-1β helper T lymphocyte epitope complex MAP vaccine for the alleviation of ulcerative colitis (Uc) in mice. The B cell epitopes of murine TNF-α (mTNF-α) were predicted in silico and coupled with the universal interleukin 1β (IL-1β) helper T-cell epitope peptide VQGEESNdK to synthesize the eight-branched MAP vaccine. Then, the immunological effects of the MAP vaccine were assessed in vitro and in vivo, as well as its impacts on dAI index, serum dAO levels, colon tissue tight junction protein amounts, ultrastructural changes, and MPO activity in BALB/c mice with Uc. The amino acids LTLRSSSQNSSdKPV at positions 78-92 of mTNF-α may constitute the dominant B cell epitope. Based on this finding, an eight-branched peptide structure, the TNF-α B-cell epitope/IL-1β helper T-cell epitope complex MAP vaccine, was synthesized. Indirect ELISA confirmed that MAP had a high affinity with commercialized mTNF-α antibodies. Meanwhile, MAP induced high specific antibody titers in vivo, reduced the dAI score, serum MPO activity, colorectal lymph node colony count, ultrastructural injuries, colon tissue histological index score and MPO activity in Uc mice, while increasing the expression levels of occludin, claudin1 and ZO1 in colon tissues. The synthetic complex MAP vaccine has good antigenicity and immunogenicity, and can alleviate Uc in mouse models.

Vaccination therapy for inflammatory bowel disease

“…This forms the base, and the outer surface of this synthetic peptide carries multiple copies of the antigen. 40 Jun Z et al found that TNF-α as an auto-component alone could not induce specific humoral immune responses, whereas the MAP strategy could significantly enhance its immunogenicity and induce specific polyclonal antibodies against TNF-α. 34 Yan S et al also found in their study that the designed eight-branched MAP vaccine possessed good immunogenicity and could The eight-branched MAP vaccine was also found to possess good immunogenicity and could exert significant anti-UC effects in the organism.…”

“… 34 Yan S et al also found in their study that the designed eight-branched MAP vaccine possessed good immunogenicity and could The eight-branched MAP vaccine was also found to possess good immunogenicity and could exert significant anti-UC effects in the organism. 40 Yang Wan and his team have found in unpublished studies that self-made TNF-α protein vaccine can overcome self-tolerance, induce specific neutralizing antibodies against TNF-α, and protect mice from acute and chronic colitis. These results may prove that therapeutic vaccines against TNF-α have a certain alleviating effect on the symptoms of IBD patients and have a certain safety profile, showing good prospects in the field of IBD treatment.…”