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[热休克蛋白增强嵌合结构(E7人乳头瘤病毒-热休克蛋白70)中包含的人乳头瘤病毒E7癌蛋白的免疫原性]

[Heat-shock protein enhances immunogenicity of E7 oncoprotein of human papillomavirus included in chimeric construction (E7 HPV-HSP70)].

作者信息

Sveshnikov P G, Solopova O N, Kurbatova E A, Shevchik Iu S, Baranovskiĭ P M, Ul'ianov A M, Bokov M N, Kiselev V I

出版信息

Zh Mikrobiol Epidemiol Immunobiol. 2010 May-Jun(3):36-9.

Abstract

AIM

To study the effect of chimeric E7 protein of human papillomavirus type 18 on activation of adaptive immunity in absence of adjuvant.

MATERIALS AND METHODS

Chimeric protein was genetically engineered and represents the protein molecule consisting of full-size E7 oncoprotein and heat-shock protein 70 (HSP70) of Mycobacterium tuberculosis in one polypeptide chain. Antibody titers as well as isotypes and subisotypes of immunoglobulins were measured by ELISA in sera of immunized animals.

RESULTS

It was shown that studied construction E7 (HPV-18)-HSP70 significantly increases titers of antibodies to E7 protein of HPV type 18 and have cross-reactive antigenic activity with E7 protein of HPV type 16. Immunization with chimeric protein resulted in increase of IgG1 and IgG2b levels and decrease of IgG2a and IgM levels.

CONCLUSION

. Oncoprotein E7 included in chimeric construction with HSP70 could be used for further studies on development of therapeutic vaccine for treatment of cervical cancer and precancerous lesions. Skew of immune response to Th2 type after intraperitoneal administration of the studied construction points to necessity for control of immunity during such studies.

摘要

目的

研究人乳头瘤病毒18型嵌合E7蛋白在无佐剂情况下对适应性免疫激活的影响。

材料与方法

对嵌合蛋白进行基因工程改造,其为一种在一条多肽链中由人乳头瘤病毒18型全尺寸E7癌蛋白和结核分枝杆菌热休克蛋白70(HSP70)组成的蛋白分子。通过酶联免疫吸附测定法(ELISA)检测免疫动物血清中的抗体滴度以及免疫球蛋白的亚型和亚亚型。

结果

研究表明,构建体E7(HPV-18)-HSP70显著提高了针对人乳头瘤病毒18型E7蛋白的抗体滴度,并且与16型人乳头瘤病毒E7蛋白具有交叉反应抗原活性。用嵌合蛋白免疫导致IgG1和IgG2b水平升高,IgG2a和IgM水平降低。

结论

与HSP70嵌合构建体中包含的癌蛋白E7可用于进一步研究开发治疗宫颈癌和癌前病变的治疗性疫苗。腹腔注射该构建体后免疫反应偏向Th2型,这表明在此类研究过程中控制免疫的必要性。

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