双价痢疾候选疫苗诱导小鼠产生粘膜免疫应答机制的初步研究

Preliminary study on the induced mucosal immuno responses of mice with the bivalent shigalla vaccine candidates

目的探讨痢疾疫苗诱导粘膜产生免疫应答的调节机制，为研制安全有效的痢疾疫苗提供免疫学的理论依据。方法以本室构建的两株福氏２ａ、宋内氏双价痢疾候选疫苗ＦＳ－２１１７与ＦＳ－５４１６经不同途径免疫小鼠，分离小鼠ＰＰ结（Ｐｅｙｅｒｓｐａｔｃｈｅｓ）与脾脏中的ＣＤ４＋Ｔ细胞并以ＭＴＴ法检测其对疫苗不同抗原成分的增殖反应。结果（１）口服痢疾疫苗可诱导ＰＰ结中的ＣＤ４＋Ｔ细胞产生显著的增殖反应，而未对脾脏中的ＣＤ４＋Ｔ细胞产生刺激作用；（２）皮下注射痢疾疫苗能使小鼠脾脏中的ＣＤ４＋Ｔ细胞产生显著的增殖反应，但未见ＰＰ结中的ＣＤ４＋Ｔ细胞产生明显的免疫应答；（３）痢疾疫苗可能有多种抗原成分参与了刺激肠粘膜ＰＰ结中ＣＤ４＋Ｔ细胞的增殖反应。结论口服痢疾候选疫苗可有效地诱导肠道粘膜产生免疫应答；免疫应答的产生可能依赖多种抗原成分的共同作用。ＰＰ结中ＣＤ４＋Ｔ细胞的特异性活化可能是诱导肠道粘膜免疫应答最重要的早期事件。

Objective To investigate the mechanism of intestinal mucosal immune response induced by shigella vaccine candidates, which would provides immunological basis for successful development of an effective and safe shigella vaccine. [WT5”HZ]Methods The mice were orally immunized with Shigella vaccine candidates,FS 2117 and FS 5416,the live attenuated bivalent hybrid strain of S.flexneri 2a and S.sonnei which were developed in this lab,and the proliferation responses of CD4 +T cells from the Peyers patches and spleen of mice were studied with MTT assay. Results (1)Significant proliferation responses to intraoral immunization of CD4 +T cells from the Peyers patches were observed through immunization by oral route but no proliferation of CD4 +T cells was found in the spleen.(2)CD4 +T cells from the spleen were proliferated through immunization by sabcutaneous routes,but no proliferation of CD4 +T cells was found in the Peyers patches.(3)Many antigen components of the shigella vaccine candidates were found to be able to induce proliferation of CD4 +T cells in Peyers patches. Conclusions Intraoral immunization with the shigella vaccine candidates can induce effective intestinal immune responses,and the immune responses may be dependent on synergetic actions of many antigen components of the shigella vaccine candidates.The specific proliferation of CD4 +T cells in Peyers patches may be an important event during the early stage of induced intestino mucosal immune responses to shigella vaccine.