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小鼠对伤寒沙门氏菌重组孔蛋白的免疫反应差异

Immune response variations to Salmonella enterica serovar Typhi recombinant porin proteins in mice.

作者信息

Toobak Hoda, Rasooli Iraj, Talei Daryush, Jahangiri Abolfazl, Owlia Parviz, Darvish Alipour Astaneh Shakiba

机构信息

Department of Biology, Shahed University, Tehran-Qom Express Way, Opposite Imam Khomeini's Shrine, Tehran 3319118651, Iran.

出版信息

Biologicals. 2013 Jul;41(4):224-30. doi: 10.1016/j.biologicals.2013.05.005. Epub 2013 Jun 21.

Abstract

OBJECTIVES

Typhoid fever is caused by Salmonella enterica serovar Typhi. OmpC, OmpF and OmpA, the three major outer membrane proteins (OMPs), could serve as vaccine candidates.

METHODS

The porins antigenicity was predicted in silico. The OMP genes were amplified, cloned and expressed. Sero-reactivities of the recombinant proteins purified by denaturing method were assayed by ELISA. BALB/c mice were immunized with the recombinant porins followed by bacterial challenge.

RESULTS

Bacterial challenge of the animal model brought about antibody triggering efficacy of the antigen in OmpF > OmpC > OmpA order. Experimental findings validated the in silico results. None of the antigens had synergic or antagonistic effects on each other from immune system induction points of view. Despite their high immunogenicity, none of the antigens was protective. However, administration of two or three antigens simultaneously resulted in retardation of lethal effect. Porins, in addition to their specific functions, share common functions. Hence, they can compensate for each other's functions.

CONCLUSIONS

The produced antibodies could not eliminate the pathogenicity by blockade of one or some of the antigens. Porin antigens are not suitable vaccine candidates alone or in denatured forms. Native forms of the antigens maybe studied for protective immunogenicity.

摘要

目的

伤寒热由伤寒沙门氏菌引起。外膜蛋白(OMP)中的三种主要蛋白,即微孔蛋白C(OmpC)、微孔蛋白F(OmpF)和外膜蛋白A(OmpA),可作为候选疫苗。

方法

通过计算机模拟预测孔蛋白的抗原性。扩增、克隆并表达OMP基因。采用酶联免疫吸附测定法(ELISA)检测经变性方法纯化的重组蛋白的血清反应活性。用重组孔蛋白免疫BALB/c小鼠,随后进行细菌攻击试验。

结果

动物模型的细菌攻击试验产生的抗体激发抗原的效力顺序为OmpF > OmpC > OmpA。实验结果验证了计算机模拟结果。从免疫系统诱导的角度来看,这些抗原之间没有协同或拮抗作用。尽管它们具有高免疫原性,但没有一种抗原具有保护作用。然而,同时给予两种或三种抗原会导致致死效应延迟。孔蛋白除了具有特定功能外,还具有共同功能。因此,它们可以相互补偿功能。

结论

产生的抗体不能通过阻断一种或某些抗原消除致病性。孔蛋白抗原单独或以变性形式都不是合适的候选疫苗。可能需要研究抗原的天然形式的保护性免疫原性。

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