title: Development of a Recombinant Xenogeneic Tumor Necrosis Factor Alpha Protein Vaccine To Protect Mice from Experimental Colitis.
abstract: Previous studies have highlighted the efficacy of tumor necrosis factor alpha (TNF-α) inhibitors, including monoclonal antibodies and soluble receptors, in the treatment and management of intestinal bowel disease (IBD). However, because of the immunogenicity of xenogeneic TNF-α inhibitors, antidrug antibodies (ADAs) can be triggered after repeated administration. An alternative way to target TNF-α is active immunization to elicit the production of high titers of neutralizing antibodies. In this study, we prepared a xenogeneic TNF-α protein vaccine and studied the protective effects in experimental colitis models. The xenogeneic TNF-α protein vaccine could overcome self-tolerance and induce TNF-α-specific neutralizing antibody. Moreover, the xenogeneic TNF-α protein vaccine could protect mice from acute and chronic colitis induced by dextran sodium sulfate (DSS). One possible explanation for this protective effect is the production of TNF-α-specific neutralizing antibody, which absorbed the biological activity of mouse TNF-α (mTNF-α) and failed to induce T lymphocyte apoptosis. In summary, use of the xenogeneic TNF-α protein vaccine may be a potent therapeutic strategy for IBD.
authors.affiliation: Department of Geriatric Medicine, No. 4 West China Teaching Hospital, Sichuan University, Chengdu, People's Republic of China State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wan
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, People's Republic of China.
authors.forename: Meng
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Cell Biology, Institute of Immunology, Medical College of Henan University, Kaifeng, People's Republic of China Department of Immunology, Key Laboratory of Cellular and Molecular Immunology, Henan University, Kaifeng, People's Republic of China.
authors.forename: Hailong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, People's Republic of China.
authors.forename: Xiuran
authors.initials: X
authors.lastname: Zheng
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, People's Republic of China.
authors.forename: Chaoheng
authors.initials: C
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, People's Republic of China.
authors.forename: Gu
authors.initials: G
authors.lastname: He
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, People's Republic of China yl.tracy73@gmail.com.
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, People's Republic of China.
authors.forename: Yuquan
authors.initials: Y
authors.lastname: Wei
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D015478:Antigens, Heterophile / Q000008:administration & dosage / Q000276:immunology; D017209:Apoptosis; D002908:Chronic Disease / Q000517:prevention & control; D016264:Dextran Sulfate / Q000008:administration & dosage; D004195:Disease Models, Animal; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D051379:Mice; D013601:T-Lymphocytes / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage* / Q000235:genetics* / Q000276:immunology; D014612:Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D015478:Antigens, Heterophile; D014409:Tumor Necrosis Factor-alpha; D014612:Vaccines; D016264:Dextran Sulfate