曹胜利, 蔡孟深, 石佑恩. 含两种不同肽段的血吸虫多抗原肽疫苗的合成及其对BALB/c小鼠的免疫保护作用J. 药学学报, 2000, 35(6): 421-425.
引用本文: 曹胜利, 蔡孟深, 石佑恩. 含两种不同肽段的血吸虫多抗原肽疫苗的合成及其对BALB/c小鼠的免疫保护作用J. 药学学报, 2000, 35(6): 421-425.
CAO Sheng-L, CAI Meng-Shen, SHI You-En. SYNTHESIS OF MULTIPLE ANTIGENIC PEPTIDE VACCINES CONTAINING TWO DIFFERENT SCHISTOSOMAL ANTIGENIC PEPTIDES AND THEIR PROTECTIVE EFFECTS ON BALB/c MICEJ. Acta Pharmaceutica Sinica, 2000, 35(6): 421-425.
Citation: CAO Sheng-L, CAI Meng-Shen, SHI You-En. SYNTHESIS OF MULTIPLE ANTIGENIC PEPTIDE VACCINES CONTAINING TWO DIFFERENT SCHISTOSOMAL ANTIGENIC PEPTIDES AND THEIR PROTECTIVE EFFECTS ON BALB/c MICEJ. Acta Pharmaceutica Sinica, 2000, 35(6): 421-425.

含两种不同肽段的血吸虫多抗原肽疫苗的合成及其对BALB/c小鼠的免疫保护作用

SYNTHESIS OF MULTIPLE ANTIGENIC PEPTIDE VACCINES CONTAINING TWO DIFFERENT SCHISTOSOMAL ANTIGENIC PEPTIDES AND THEIR PROTECTIVE EFFECTS ON BALB/c MICE

  • 摘要: 目的 设计合成由曼氏血吸虫28 KDa GST抗原肽段26-43(P26), 116-131(P116), 141-153(P141)和日本血吸虫26 KDa GST抗原肽段187-202(J187)中的两种不同肽段组成的血吸虫混合多抗原肽疫苗,通过活性试验考察其抗原性、免疫原性及对BALB/c小鼠的保护性免疫效果。方法 用Boc化学和Fmoc化学相结合的策略合成含两种不同抗原肽的多抗原肽疫苗,产物经斑点酶联免疫吸附试验测定抗原性,在无免疫佐剂存在下接种小鼠,ELISA试验检测血清抗体,并用日本血吸虫尾蚴攻击感染,6周后剖杀小鼠进行体内成虫和肝内虫卵计数。结果和结论 合成的混合多抗原肽能够与感染日本血吸虫的病人或病兔血清结合,并能诱导BALB/c小鼠产生对日本血吸虫天然抗原特异的抗体应答。且合成的混合多抗原肽疫苗能够诱导BALB/c小鼠产生显著的抗日本血吸虫感染的保护性免疫力,这种免疫力不仅降低成虫负荷数,还能显著减少肝组织内虫卵检获数,其中(P116)4(P26)4-MAP的减虫率和减卵率均达70%以上,因此有希望发展成为有效的抗血吸虫疫苗。

     

    Abstract: AIM Three multiple antigenic peptide(MAP) vaccines, (P116)4(P26)4-MAP, (P116)4(P141)4-MAP and (P26)4(J187)4-MAP, in which P26, P116, and P141 are, respectively, the residue 26-43(AAGVDYEDERISFQDWPK), 116-131(PQEEKEKITKEILNGK) and 141-153(ESLKGSTGKLAVG) of 28 KDa glutathione S-tranferase of Schistosoma mansoni(Sm28GST), and J187 is the residue 187-202(PQIDKYLKSSKYIAWP) of 26 KDa glutathione S-tranferase of Schistosoma japonicum(Sj26GST), have been designed for examination of their antigenicities, immunogenicities and protective effects on BALB/c mice. METHODS The multiple antigenic peptide vaccines consisting of two different antigenic peptides have been synthesized using both Boc and Fmoc chemistry and their antigenicities have been tested with dot-ELISA. Mice were bled to test antibody responses after vaccination with the synthetic MAPs, and were infected with Schistosoma japonicum cercariae. Six weeks after infection, the mice were killed to recover adult worms and eggs in the liver. RESULTS AND CONCLUSION The synthetic MAPs consisting of two different schistosomal antigenic peptides was shown to be bound by both patient and infected-rabbit sera, and were able to elicit antibody responses specific to natural antigen of Schistoma japonicum. Furthermore, BALB/c mice vaccinated with the synthetic MAPs were significantly protected against the challenge infection with Schistosoma japonicun cercaria. Especially, immunization with (P116)4(P26)4-MAP reduced the worm burden in BALB/c mice by 73.6% and liver eggs by 75.9%. Therefore, it will be useful for the development of effective anti-schistosome vaccine.

     

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