IntroductionTumor necrosis factor-⍺ (TNF⍺) is central to the pathogenesis of autoimmune and inflammatory diseases, and monoclonal antibody-based TNF⍺ inhibitors are amongst the most used biologics worldwide. As an alternative to exogenously administered antibodies, active immunization has been explored as a TNF⍺ neutralization strategy.MethodsWe generated a murine TNF⍺ (mTNF⍺) Y87S point mutant expressed in E.
coli that preserved the native trimeric structure while abrogating receptor binding. Using histidine-tag interactions, the antigen was displayed on the surface of immunogenic cobalt porphyrin-phospholipid (CoPoP) liposomes, which further attenuated TNF⍺ toxicity and enabled safe immunization.
Immunization and protective efficacy were evaluated in murine models, including lipopolysaccharide/galactosamine-induced lethal shock and collagen-induced arthritis (CIA). Parallel studies were conducted with a similarly engineered human TNF⍺ (hTNF⍺) Y87S mutant.ResultsLiposome display of TNF⍺ elicited significantly higher levels of neutralizing antibodies following immunization.
In mice, immunization improved survival in the lethal shock model and ameliorated clinical symptoms and joint inflammation in the CIA model. The Y87S mutation similarly detoxified hTNF⍺ constructs, which could also be effectively displayed on CoPoP liposomes.
Frontiers in Immunology published a clinical update in Infectious Disease on 10 Apr 2026.
The item focuses on Immunization with detoxified TNFα elicits neutralizing antibodies and ameliorates inflammatory shock and autoimmune arthritis in mice.
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