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The oral cholera vaccine WC-rBS consists of 4 different inactivated strains of Vibrio cholerae (LPS source) admixed with recombinant cholera toxin B subunit. Because of its unique composition and anti-inflammatory properties reported for both CTB and low doses of LPS from other Gram-negative bacteria, we speculated that WC-rBS might have anti-inflammatory potential in a chronic autoimmune disease such as inflammatory bowel diseases. First in vitro endotoxin tolerance experiments showed the surprising WC-rBS potential in the modulation of inflammatory responses on both PBMCs and THP1 cells. WC-rBS was further evaluated in the Dextran Sodium Sulfate colitis mouse model. Administrated orally at different dosages, WC-rBS vaccine was safe and showed immunomodulatory properties when administered in a preventive mode (before and during the induction of DSS colitis) as well as in a curative mode (after colitis induction); with improvement of disease activity index (from 27 to 73%) and histological score (from 65 to 88%). Interestingly, the highest therapeutic effect of WC-rBS vaccine was observed with the lowest dosage, showing even better anti-inflammatory properties than mesalamine; an approved 5-aminosalicylic acid drug for treating IBD patients. In summary, this is the first time that a prophylactic medicine, safe and approved for prevention of an infectious disease, showed a benefit in an inflammatory bowel disease model, potentially offering a novel therapeutic modality for IBD patients.

口服霍乱疫苗WC-rBS由4株不同的灭活霍乱弧菌（脂多糖（Lipopolysaccharide, LPS）来源）菌株混合重组霍乱毒素B亚基（recombinant cholera toxin B subunit）制成。鉴于其独特的组分，以及霍乱毒素B亚基（CTB）与其他革兰氏阴性菌来源的低剂量LPS均已被报道具有抗炎特性，我们推测WC-rBS或许在慢性自身免疫性疾病（如炎症性肠病（Inflammatory Bowel Disease, IBD））中具备抗炎潜力。首批体外内毒素耐受实验便显示，WC-rBS可对人外周血单个核细胞（Peripheral Blood Mononuclear Cells, PBMC）与THP1细胞的炎症反应发挥调控作用，其效果令人意外。研究团队进一步在葡聚糖硫酸钠（Dextran Sodium Sulfate, DSS）结肠炎小鼠模型中对WC-rBS开展了评估。以不同剂量口服给药时，WC-rBS疫苗安全性良好，且在预防给药方案（DSS结肠炎造模前及造模过程中）与治疗给药方案（结肠炎造模后）中均展现出免疫调节活性；可使疾病活动指数改善27%至73%，组织学评分改善65%至88%。值得注意的是，WC-rBS疫苗在最低剂量下便展现出最优治疗效果，其抗炎活性甚至优于美沙拉嗪——一款获批用于治疗IBD患者的5-氨基水杨酸（5-aminosalicylic acid, 5-ASA）类药物。综上，本研究首次证实一款已获批用于预防传染病的安全预防性药物，可在IBD模型中展现出治疗获益，有望为IBD患者提供全新的治疗策略。