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目的研制多价、安全、高效和无抗生素抗性的志贺氏菌疫苗。方法利用动物模型，评价志贺氏菌双价（Ｓ．ｆｌｅｘｎｅｒｉ２ａ－Ｓ．ｄｙｓｅｎｔｅｒｉａｅＩ）疫苗候选株ＤＯＭ３的残余毒力、免疫原性和保护力。结果ＤＯＭ３的残余毒力分别比野生型毒株Ｓ．ｆｌｅｘｎｅｒｉ２ａ３０１和Ｓ．ｄｙｓｅｎｔｅｒｉａｅＩ１１２低１２０倍和５７倍（昆明系小鼠），８７３和１９５倍（ＳＰＦＢＡＬＢ／ｃ小鼠）。ＤＯＭ３丧失了侵袭上皮细胞的能力。ＤＯＭ３具有和Ｓ．ｆｌｅｘｎｅｒｉ２ａ３０１几乎相同的免疫原性，但较Ｓ．ｄｙｓｅｎｔｅｒｉａｅＩ１１２的免疫原性略差。皮下免疫小鼠血清中特异性抗体ＩｇＡ、ＩｇＧ滴度峰值出现在最后一次皮下注射的第２周，而ＩｇＭ滴度峰值出现在第１周，然后滴度逐步下降，在６周后趋于稳定。血清中同时具有抗Ｓ．ｆｌｅｘｎｅｒｉ２ａ菌和抗Ｓ．ｄｙｓｅｎｔｅｒｉａｅＩ菌的抗体，且其滴度变化的趋势基本一致。使用昆明系小鼠，以３０ＬＤ５０（６．１３×１０７ＣＦＵ）的野生型毒株Ｓ．ｆｌｅｘｎｅｒｉ２ａ３０１和２１ＬＤ５０（６．２６×１０７ＣＦＵ）野生型毒株Ｓ．ｄｙｓｅｎｔｅｒｉａｅＩ１１２攻击，保护率分别为９０％和７０％；使用ＳＰＦＢＡＬＢ?
Objective To develop a multivalent, safe, efficient and antibiotic-free Shigella vaccine. Methods Animal models were used to evaluate the residual virulence, immunogenicity and protective ability of DOM3, a candidate strain of S.flexneri 2a-S. dysenteriae I vaccine. Results DOM3 residual virulence than wild-type strain S. flexneri2a301 and S. 120-fold and 57-fold lower (Kunming mice), 873 and 195-fold (SPFBALB / c mice) of dysenteriae I112. DOM3 loses the ability to invade epithelial cells. DOM3 has sum S. Flexneri2a301 has almost the same immunogenicity but is more than S. The immunogenicity of dysenteriaeI112 is slightly worse. The peak of IgA and IgG titers in serum of subcutaneous immunized mice appeared in the second week of the last subcutaneous injection, while the peak of IgM titers appeared in the first week, then the titer decreased gradually and tended to be stable after 6 weeks . Anti-S in serum at the same time. flexneri2a bacteria and anti-s Antibodies of dysenteriae I bacteria, and the trend of their titer changes are basically the same. Kunming mice were used with a 30LD50 (6.13 x 107 CFU) of wild type strain S. Flexneri2a 301 and 21 LD50 (6.26 × 107 CFU) wild-type strain S. dysenteriaeI112 attack, protection rates were 90% and 70%; use SPFBALB?