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: Yang Wan, Meng Li, Hailong Zhang, Xiuran Zheng, Chaoheng Yu, Gu He, Yan Luo, Li Yang, Yuquan Wei
• Journal: Clinical and vaccine immunology : CVI (Clin Vaccine Immunol) Vol. 22 Issue 12 Pg. 1269-75 (Dec 2015) ISSN: 1556-679X [Electronic] United States
• PMID: 26466602 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Chemical References

• Antibodies, Neutralizing
• Antigens, Heterophile
• Tumor Necrosis Factor-alpha
• Vaccines
• Dextran Sulfate

Topics

• Animals
• Antibodies, Neutralizing (blood)
• Antigens, Heterophile (administration & dosage, immunology)
• Apoptosis
• Chronic Disease (prevention & control)
• Dextran Sulfate (administration & dosage)
• Disease Models, Animal
• Inflammatory Bowel Diseases (chemically induced, prevention & control)
• Male
• Mice
• T-Lymphocytes (physiology)
• Tumor Necrosis Factor-alpha (administration & dosage, genetics, immunology)
• Vaccines (administration & dosage, genetics, immunology)