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

Sun,Yan; Pan,Wensheng; Zhang,Jun; Cui,Ying; Wang,Huiju; Ru,Guoqing; Chen,Legao

doi:10.3892/ijmm.2019.4271

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

Authors:
- Yan Sun
- Wensheng Pan
- Jun Zhang
- Ying Cui
- Huiju Wang
- Guoqing Ru
- Legao Chen
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Affiliations: The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, P.R. China, Department of Gastroenterology, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310014, P.R. China, Department of Nuclear Medicine, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310014, P.R. China, Key Laboratory of Gastroenterology of Zhejiang Province, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310014, P.R. China, Department of Pathology, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310014, P.R. China, Department of Vascular Surgery, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310014, P.R. China
Published online on: July 8, 2019 https://doi.org/10.3892/ijmm.2019.4271
Pages: 1106-1116

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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.

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