Addition of CpG ODN to recombinant Pseudomonas aeruginosa ExoProtein A conjugates of AMA1 and Pfs25 greatly increases the number of responders
Addition of CpG ODN to recombinant Pseudomonas aeruginosa ExoProtein A conjugates of AMA1 and Pfs25 greatly increases the number of responders
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DOI：
10.1016/j.vaccine.2008.03.005
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发表时间：
2008-05-12
期刊：
影响因子：
5.5
通讯作者：
Mullen, Gregory E. D.
中科院分区：
文献类型：
--
作者：
Qian, Feng;Rausch, Kelly M.;Mullen, Gregory E. D.
恶性疟原虫的血液阶段蛋白质顶端膜抗原1（AMA 1）和25-kDa性阶段蛋白质（Pfs 25）是疟疾疫苗开发中的两个主要候选者。我们以前已经证明，这些疟疾抗原的重组铜绿假单胞菌胞外蛋白A（rEPA）的共轭显着增加了小鼠的平均特异性功能性抗体反应，然而，一些小鼠的反应不佳，无法证明功能性反应。我们假设，这两种疟疾抗原的免疫原性可以通过在制剂中包含CpG寡脱氧核苷酸来进一步增强。用在添加或不添加CPG 7909的Alhydrogel上配制的rEPA缀合或未缀合的AMA 1和Pfs 25免疫小鼠。小鼠在第0天和第28天接受制剂，并在第42天收集小鼠血清。对这些血清的ELISA分析显示，将CPG 7909添加到在Alhydrogel上配制的AMA 1-rEPA和Pfs 25-rEPA中诱导的平均抗体滴度显著高于不含CPG 7909的制剂，并导致混合的Th 1/Th 2应答，如小鼠IgG 1和IgG 2a亚类的产生所证明的。CPG 7909在两种缀合抗原的制剂中的存在大大增加了抗体滴度足以在体外抑制血液阶段寄生虫生长或阻断性阶段寄生虫向蚊子传播的应答者的比例。在这项研究中获得的结果表明，潜在的使用组合策略，以增加对疟疾抗原在人类中的应答者的数量。爱思唯尔有限公司出版
Both the blood-stage protein apical membrane antigen 1 (AMA1) and the 25-kDa sexual-stage protein (Pfs25) of Plasmodium falciparum are two leading candidates in malarial vaccine development. We have previously demonstrated that conjugation of these malarial antigens to recombinant Pseudomonas aeruginosa ExoProtein A (rEPA) significantly increased the mean-specific functional antibody responses in mice; however, some mice responded poorly and were unable to demonstrate a functional response. We hypothesized that the immuno-genicities of these two malarial antigens could be further enhanced by the inclusion of a CpG oligodeoxynucleotide in the formulation. Mice were immunized with either rEPA-conjugated or unconjugated AMA1 and Pfs25 formulated on Alhydrogel with or without the addition of CPG 7909. Mice received the formulations on days 0 and 28, and mouse sera were collected on day 42. ELISA analyses on these sera showed that the addition of CPG 7909 to AMA1-rEPA and Pfs25-rEPA formulated on Alhydrogel induced significantly higher mean antibody titers than the formulations without CPG 7909, and led to a mixed Th1/Th2 response as demonstrated by the production of mouse IgG1 and IgG2a subclasses. The presence of CPG 7909 in the formulations of both conjugated antigens greatly increased the proportion of responders with antibody titers sufficient to inhibit blood-stage parasite growth in vitro or block transmission of sexual-stage parasites to mosquitoes. The results obtained in this study indicate the potential use of a combination strategy to increase the number of responders to malarial antigens in humans. Published by Elsevier Ltd.