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用无佐剂形式的重组糖蛋白D-白细胞介素-2融合蛋白对2型单纯疱疹病毒急性和复发性感染进行免疫治疗。

Immunotherapy of acute and recurrent herpes simplex virus type 2 infection with an adjuvant-free form of recombinant glycoprotein D-interleukin-2 fusion protein.

作者信息

Nakao M, Hazama M, Mayumi-Aono A, Hinuma S, Fujisawa Y

机构信息

Pharmaceutical Research and Discovery Research Divisions, Takeda Chemical Industries, Osaka, Japan.

出版信息

J Infect Dis. 1994 Apr;169(4):787-91. doi: 10.1093/infdis/169.4.787.

DOI:10.1093/infdis/169.4.787
PMID:8133093
Abstract

Previous studies demonstrated that the adjuvant-free form of a fusion protein consisting of a truncated herpes simplex virus type 1 (HSV-1) glycoprotein D and human interleukin-2 (tgD-IL-2) elicited superior protective immunity in mice. In this study, the immunotherapeutic efficacy of tgD-IL-2 against vaginal HSV-2 infection was investigated using a guinea pig model. Footpad injections of tgD-IL-2 (12.5 micrograms/dose) after the onset of primary lesions strongly suppressed recurrence in the chronic phase of infection; consequently, the number of days with lesions was reduced 65%. Continuous medication with 100 mg/kg/day acyclovir for 5 days failed to suppress recurrent infection. In a UV radiation-induced recurrence model, prophylactic tgD-IL-2 significantly suppressed both duration and severity of disease. A single injection of tgD-IL-2 plus acyclovir produced an additive effect on the suppression of the disease in the acute phase. These results suggest that tgD-IL-2 is a promising immunotherapeutic agent against HSV-2 genital infections.

摘要

先前的研究表明,由截短的单纯疱疹病毒1型(HSV-1)糖蛋白D和人白细胞介素-2组成的融合蛋白(tgD-IL-2)的无佐剂形式在小鼠中引发了卓越的保护性免疫。在本研究中,使用豚鼠模型研究了tgD-IL-2对阴道HSV-2感染的免疫治疗效果。在原发性损伤出现后,通过足垫注射tgD-IL-2(12.5微克/剂量)可强烈抑制感染慢性期的复发;因此,出现损伤的天数减少了65%。连续5天给予100毫克/千克/天的阿昔洛韦未能抑制复发性感染。在紫外线辐射诱导的复发模型中,预防性给予tgD-IL-2可显著抑制疾病的持续时间和严重程度。单次注射tgD-IL-2加阿昔洛韦在急性期对疾病的抑制产生了相加作用。这些结果表明,tgD-IL-2是一种有前景的针对HSV-2生殖器感染的免疫治疗药物。

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Immunotherapy of acute and recurrent herpes simplex virus type 2 infection with an adjuvant-free form of recombinant glycoprotein D-interleukin-2 fusion protein.用无佐剂形式的重组糖蛋白D-白细胞介素-2融合蛋白对2型单纯疱疹病毒急性和复发性感染进行免疫治疗。
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Antibody-cytokine fusion proteins: applications in cancer therapy.
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