Molecular adjuvant HMGB1 enhances anti-influenza immunity during DNA vaccination.
Molecular adjuvant HMGB1 enhances anti-influenza immunity during DNA vaccination.
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作者：
基于DNA的疫苗虽然在小鼠中具有高度免疫原性，但在灵长类动物中产生的反应明显较弱。因此，目前的努力旨在增加其免疫原性，包括优化质粒/基因、疫苗制剂和递送方法。例如，用编码免疫调节蛋白的分子佐剂共免疫已显示出改善抗原（Ag）特异性免疫应答。因此，诸如这些的增强元件的掺入在其中高滴度抗体（Ab）应答对于保护是关键的流感模型中可能是特别重要的。在这方面，我们比较了质粒编码的高迁移率族蛋白1蛋白（HMGB 1），一种新的细胞因子，我们以前已经突变，以增加DNA疫苗的免疫原性，与加强Ag特异性免疫反应在DNA疫苗接种期间与流感病毒A/PR/8/34核蛋白或血凝素的一种新的H1N1/09。我们表明，HMGB 1佐剂能够增强适应性效应和记忆免疫应答。尽管在所有接种疫苗的动物中均检测到Ag特异性抗体，但更大的中和Ab应答与HMGB 1佐剂相关。此外，这些应答改善了CD 8 T+细胞效应子和记忆应答，并提供了针对致死性粘膜流感A/PR/8/34攻击的保护。因此，与HMGB 1的共免疫在针对质粒编码的Ag的免疫的发展期间具有强的体内佐剂活性。
DNA-based vaccines, while highly immunogenic in mice, generate significantly weaker responses in primates. Therefore, current efforts are aimed at increasing their immunogenicity, which include optimizing the plasmid/gene, the vaccine formulation and method of delivery. For example, co-immunization with molecular adjuvants encoding an immunomodulatory protein has been shown to improve the antigen (Ag)-specific immune response. Thus, the incorporation of enhancing elements, such as these, may be particularly important in the influenza model in which high titered antibody (Ab) responses are critical for protection. In this regard, we compared the ability of plasmid-encoded high-mobility group box 1 protein (HMGB1), a novel cytokine in which we have previously mutated in order to increase DNA vaccine immunogenicity, with boost Ag-specific immune responses during DNA vaccination with influenza A/PR/8/34 nucleoprotein or the hemagglutinin of A novel H1N1/09. We show that the HMGB1 adjuvant is capable of enhancing adaptive effector and memory immune responses. Although Ag-specific antibodies were detected in all vaccinated animals, a greater neutralizing Ab response was associated with the HMGB1 adjuvant. Furthermore, these responses improved CD8 T+-cell effector and memory responses and provided protection against a lethal mucosal influenza A/PR/8/34 challenge. Thus, co-immunization with HMGB1 has strong in vivo adjuvant activity during the development of immunity against plasmid-encoded Ag.
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影响因子：
6.4
作者：
通讯作者：
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通过合成共识DNA抗原的体内电穿孔对致病性人类和鸟类流感病毒的杂型保护。
影响因子：
3.7
作者：
Laddy, Dominick J.;Yan, Jian;Kutzler, Michele;Kobasa, Darwyn;Kobinger, Gary P.;Khan, Amir S.;Greenhouse, Jack;Sardesai, Niranjan Y.;Draghia-Akli, Ruxandra;Weiner, David B.
通讯作者：
Weiner, David B.
DOI：
10.1038/nrg2432
发表时间：
2008-10
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
--
影响因子：
5.5
作者：
Lin, Feng;Shen, Xuefei;Sardesai, Niranjan Y.
通讯作者：
Sardesai, Niranjan Y.
影响因子：
3.1
作者：
Khan, AS;Smith, LC;Draghia-Akli, R
通讯作者：
Draghia-Akli, R