| Target Validation Information | |||||
|---|---|---|---|---|---|
| Target ID | T77664 | ||||
| Target Name | Interferon gamma | ||||
| Target Type | Clinical Trial |
||||
| Drug Potency against Target | Fontolizumab | Drug Info | IC50 = 10 ug/ml | ||
| Action against Disease Model | Fontolizumab | Fontoliz uMab inhibited IFN-c-induced IP-10 production in a susceptible cell line, which can be nuetralized by anti-fontoliz uMab antibodies | [552585] | Drug Info | |
| The Effect of Target Knockout, Knockdown or Genetic Variations | Venezuelan equine encephalitis virus replicon particles (VRP) expressing the hemagglutinin (HA) gene from influenza virus (HA-VRP) were used to vaccinate both wildtype (wt) and IFN alpha/beta receptor knockout (RKO) mice. HA-VRP vaccination induced equivalent levels of flu-specific systemic IgG, mucosal IgG, and systemic IgA antibodies in both wt and IFN RKO mice. In contrast, HA-VRP vaccination of IFN RKO mice failed to induce significant levels of flu-specific mucosal IgA antibodies at multiple mucosal surfaces. In the VRP adjuvant system, co-delivery of null VRP with ovalb uMin (OVA) protein significantly increased the levels of OVA-specific ser uM IgG, fecal IgG, and fecal IgA antibodies in both wt and RKO mice, suggesting that type I IFN signaling plays a less significant role in the VRP adjuvant effect. Taken together, these results suggest that (1) at least in regard to IFN signaling, the mechanisms which regulate alphavirus-induced immunity differ when VRP are utilized as expression vectors as opposed to adjuvants, and (2) type I IFN signaling is required for the induction of mucosal IgA antibodies directed against VRP-expressed antigen. These resultsshed new light on the regulatory networks which promote immune induction, and specifically mucosal immune induction, with alphavirus vaccine vectors | [552585] | |||
| References | |||||
| Ref 552585 | Fontolizumab, a humanised anti-interferon gamma antibody, demonstrates safety and clinical activity in patients with moderate to severe Crohn's disease. Gut. 2006 Aug;55(8):1131-7. Epub 2006 Feb 28. | ||||
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