双价痢疾工程疫苗经粘膜免疫动物的实验研究

The experimental study of two bivalent Shigella vaccines immunized mice in different mucosal route

目的 探讨不同粘膜免疫途径对 2株痢疾工程疫苗免疫效果的影响。方法 用FSM 2 1 1 7或FS 54 1 6以 4× 1 0 7CFU/只分别经滴鼻、灌胃和小肠内免疫小鼠 ,3次免疫后 7d分离小鼠脾、派伊尔结 (PP)、肠系膜中心淋巴结 (MLN)、小肠淋巴细胞固有层 (LPL)、鼻通道 (NP)及NALT淋巴细胞 ,用BA ELISASPOT法检测其特异性抗FSM 2 1 1 7或FS 54 1 6全菌抗原的IgA、IgG ASC(抗体分泌细胞 )数量。结果 2株疫苗经鼻内免疫都诱发了鼻粘膜相关淋巴组织、胃肠粘膜相关淋巴组织以及代表系统免疫反应的脾淋巴细胞全菌抗原特异性IgA、IgG ASC的显著增加 (P <0 .0 5和 0 .0 1 )。小肠内免疫后 ,可有效诱发肠粘膜局部以及脾淋巴细胞全菌抗原特异性IgA、IgG ASC的显著增加 (P <0 .0 1 ) ,但不能刺激鼻粘膜局部淋巴细胞的特异性ASC反应。结论 2株疫苗经鼻粘膜免疫均可诱导NALT和GALT及系统免疫反应的发生 ,是一个可行的免疫途径。

Objective To observe the effect of three different mucosal routes on the induction of immunogenicity of two bivalent Shigella vaccines. Methods BALB/c mice were divided into three groups with 10 in each. Mice were respectively immunized with Ipa + or Ipa - vaccines(4×10 7CFU) three doses with interval of two weeks by intranasal, intragastric or intraintestinal routes. The spleen, PP, MLN, LPL, NP, NALT lymphocytes were isolated on seventh day at random after last immunization. An BA ELISASPOT was done to quantify specific IgA or IgG ASC against bacteria pan antigen. Results The production of IgA and IgG ASC of spleen, GALT and NALT lymphocytes of intranasal group was significantly increased. In intraintestinal group, IgA and IgG ASC of spleen, GALT lymphocytes were significantly increased; but NALT lymphocytes did not increase. Conclusion Two bivalent Shigella vaccines can induce spleen immune response in NALT, GALT by intranasal inoculation. Only GALT but not NALT response was induced by intraintestinal inoculation.