Complex TNF-[alpha] B cell epitope MAP vaccine alleviates murine ulcerative colitis

The present study aimed to develop a tumor necrosis factor-[alpha] (TNF-[alpha]) B-cell epitope/IL-1[beta] helper T lymphocyte epitope complex MAP vaccine for the alleviation of ulcerative colitis (UC) in mice. The B cell epitopes of murine TNF-[alpha] (mTNF-[alpha]) were predicted in silico and coupled with the universal interleukin 1[beta] (IL-1[beta]) 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 LTLRS S SQNS SDKPV at positions 78-92 of mTNF-[alpha] may constitute the dominant B cell epitope. Based on this finding, an eight-branched peptide structure, the TNF-[alpha] B-cell epitope/IL-1[beta] helper T-cell epitope complex MAP vaccine, was synthesized. Indirect ELISA confirmed that MAP had a high affinity with commercialized mTNF-[alpha] 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, claudinl and ZOl in colon tissues. The synthetic complex MAP vaccine has good antigenicity and immunogenicity, and can alleviate UC in mouse models.