Development of a Recombinant Xenogeneic Tumor Necrosis Factor Alpha Protein Vaccine To Protect Mice from Experimental Colitis

Abstract

dPrevious studies have highlighted the efficacy of tumor necrosis factor alpha (TNF-␣) 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-␣ inhibitors, antidrug antibodies (ADAs) can be triggered after repeated administration. An alternative way to target TNF-␣ is active immunization to elicit the production of high titers of neutralizing antibodies. In this study, we prepared a xenogeneic TNF-␣ protein vaccine and studied the protective effects in experimental colitis models. The xenogeneic TNF-␣ protein vaccine could overcome self-tolerance and induce TNF-␣-specific neutralizing antibody. Moreover, the xenogeneic TNF-␣ 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-␣-specific neutralizing antibody, which absorbed the biological activity of mouse TNF-␣ (mTNF-␣) and failed to induce T lymphocyte apoptosis. In summary, use of the xenogeneic TNF-␣ protein vaccine may be a potent therapeutic strategy for IBD.

Aconitine induces cardiomyocyte damage by mitigating BNIP3‐dependent mitophagy and the TNFα‐NLRP3 signalling axis

“…Moreover, the NLR (Nod‐like receptor) signalling pathway, apoptosis and regulation of autophagy pathways were top‐ranked pathways enriched by GSEA analysis (Figure C). Several inflammation‐related genes, such as TNF, IL‐1β and NLRP3, were common among these enriched pathways …”

“…Several inflammation-related genes, such as TNF, IL-1β and NLRP3, were common among these enriched pathways. 19,[33][34][35]…”

Potencial terapêutico da saliva de Aedes aegypti na inflamação intestinal experimental

“…O efeito protetor da inibição in vivo de TNF-α na progressão da inflamação intestinal foi também observado em modelos experimentais utilizando DSS. Nesse sentido, um trabalho recente, demonstrou por meio da produção de anticorpos anti-TNF, a eficácia da neutralização dessa citocina em camundongos, na melhora clínica da inflamação intestinal induzida por DSS [146]. Outros trabalhos utilizando diferentes abordagens terapêuticas, também mostraram melhora na condição clínica dos camundongos associada à redução dos níveis de TNF [129,147].…”