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霍乱毒素B亚基基因与DNA疫苗皮内共同给药时,可增强黏膜免疫球蛋白A、Th1型和CD8+细胞毒性反应。

Cholera toxin B-subunit gene enhances mucosal immunoglobulin A, Th1-type, and CD8+ cytotoxic responses when coadministered intradermally with a DNA vaccine.

作者信息

Sanchez Alba E, Aquino Guillermo, Ostoa-Saloma Pedro, Laclette Juan P, Rocha-Zavaleta Leticia

机构信息

Department of Molecular Biology and Biotechnology, Institute of Biomedical Research, National University of Mexico, Mexico D.F. 04510, Mexico.

出版信息

Clin Diagn Lab Immunol. 2004 Jul;11(4):711-9. doi: 10.1128/CDLI.11.4.711-719.2004.

Abstract

A plasmid vector encoding the cholera toxin B subunit (pCtB) was evaluated as an intradermal genetic adjuvant for a model DNA vaccine expressing the human papillomavirus type 16 L1 capsid gene (p16L1) in mice. p16L1 was coadministered with plasmid pCtB or commercial polypeptide CtB as a positive control. Coadministration of pCtB induced a significant increment of specific anti-L1 immunoglobulin A (IgA) antibodies in cervical secretions (P < 0.05) and fecal extracts (P < 0.005). Additionally, coadministration of pCtB enhanced the production of interleukin-2 and gamma interferon by spleen cells but did not affect the production of interleukin-4, suggesting a Th1-type helper response. Furthermore, improved CD8+ T-cell-mediated cytotoxic activity was observed in mice vaccinated with the DNA vaccine with pCtB as an adjuvant. This adjuvant effect was comparable to that induced by the CtB polypeptide. These results indicate that intradermal coadministration of pCtB is an adequate means to enhance the mucosa-, Th1-, and CD8(+)-mediated cytotoxic responses induced by a DNA vaccine.

摘要

编码霍乱毒素B亚基的质粒载体(pCtB)被评估作为一种皮内基因佐剂,用于在小鼠中表达人乳头瘤病毒16型L1衣壳基因的模型DNA疫苗(p16L1)。p16L1与质粒pCtB或作为阳性对照的商业多肽CtB共同给药。pCtB的共同给药诱导宫颈分泌物(P < 0.05)和粪便提取物(P < 0.005)中特异性抗L1免疫球蛋白A(IgA)抗体显著增加。此外,pCtB的共同给药增强了脾细胞白细胞介素-2和γ干扰素的产生,但不影响白细胞介素-4的产生,提示Th1型辅助反应。此外,在用pCtB作为佐剂的DNA疫苗接种的小鼠中观察到改善的CD8 + T细胞介导的细胞毒性活性。这种佐剂效应与CtB多肽诱导的效应相当。这些结果表明,皮内共同给药pCtB是增强DNA疫苗诱导的粘膜、Th1和CD8(+)介导的细胞毒性反应的适当手段。

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