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一种含CpG的寡脱氧核苷酸作为有效的佐剂,可平衡白喉-破伤风-百日咳疫苗中的Th1/Th2免疫反应。

A CpG-containing oligodeoxynucleotide as an efficient adjuvant counterbalancing the Th1/Th2 immune response in diphtheria-tetanus-pertussis vaccine.

作者信息

Sugai Toshiyuki, Mori Masaaki, Nakazawa Masatoshi, Ichino Motohide, Naruto Takuya, Kobayashi Naoki, Kobayashi Yoshinori, Minami Mutsuhiko, Yokota Shumpei

机构信息

Department of Pediatrics, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa 236-0004, Japan.

出版信息

Vaccine. 2005 Nov 16;23(46-47):5450-6. doi: 10.1016/j.vaccine.2004.09.041. Epub 2005 Jun 21.

DOI:10.1016/j.vaccine.2004.09.041
PMID:16006019
Abstract

Adjuvants in vaccines are immune stimulants that play an important role in the induction of effective and appropriate immune responses to vaccine component(s). Diphtheria-tetanus-pertussis (DPT) vaccine contains not only aluminum hydrate (alum) to enhance the immune response to the vaccine ingredients, but also, both for that purpose and as a principal ingredient, pertussis toxin (PT). However, both adjuvants strongly promote T helper (Th) 2 type immune responses. Th1 and Th2 type immune responses are counterbalanced in vivo, and a Th2-prone immune response is not effective against intracellular infections but promotes IgE production, which is related to allergic disease. In this study, we used the CpG motif contained in oligodeoxynucleotide (CpG-ODN), which has an adjuvant effect and also induces the Th1 response, as an adjuvant to this vaccine, and we investigated its adjuvanticity and its potential to modulate immune responses to DPT vaccine. Administration of DPT vaccine with CpG-ODN (DPT-alum/ODN) to mice significantly reduced the total IgE levels and increased the anti-PT specific IgG2a titer in serum, in comparison with ordinary DPT vaccine (DPT-alum). Moreover, we investigated the antibody response to orally administrated ovalbumin (OVA) after vaccine administration. In the DPT-alum/ODN-administered group, the OVA specific IgE production in serum greatly decreased in comparison with that in the DPT-alum-administered group. These data indicate that CpG-ODN was not useful only as an efficient vaccine adjuvant but also shifted the immune responses substantially toward Th1 and modulated the Th1/Th2 immune response in DPT vaccine. These data suggested new applications of CpG-ODN as adjuvants in DPT vaccine.

摘要

疫苗中的佐剂是免疫刺激剂,在诱导针对疫苗成分产生有效且适当的免疫反应中发挥重要作用。白喉-破伤风-百日咳(DPT)疫苗不仅含有水合铝(明矾)以增强对疫苗成分的免疫反应,而且为了该目的以及作为主要成分,还含有百日咳毒素(PT)。然而,这两种佐剂都强烈促进辅助性T(Th)2型免疫反应。Th1和Th2型免疫反应在体内相互平衡,倾向于Th2的免疫反应对细胞内感染无效,但会促进与过敏性疾病相关的IgE产生。在本研究中,我们使用寡脱氧核苷酸(CpG-ODN)中含有的CpG基序作为该疫苗的佐剂,其具有佐剂作用且还能诱导Th1反应,我们研究了其佐剂活性以及调节对DPT疫苗免疫反应的潜力。与普通DPT疫苗(DPT-明矾)相比,给小鼠接种含CpG-ODN的DPT疫苗(DPT-明矾/ODN)可显著降低血清中总IgE水平并提高抗PT特异性IgG2a滴度。此外,我们研究了接种疫苗后对口服卵清蛋白(OVA)的抗体反应。与接种DPT-明矾的组相比,接种DPT-明矾/ODN的组血清中OVA特异性IgE产生大幅下降。这些数据表明,CpG-ODN不仅是一种有效的疫苗佐剂,而且还能使免疫反应显著转向Th1,并调节DPT疫苗中的Th1/Th2免疫反应。这些数据提示了CpG-ODN作为DPT疫苗佐剂的新应用。

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