Plasmodium berghei circumvents immune responses induced by merozoite surface protein 1- and apical membrane antigen 1-based vaccines.
Plasmodium berghei circumvents immune responses induced by merozoite surface protein 1- and apical membrane antigen 1-based vaccines.
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DOI：
10.1371/journal.pone.0013727
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发表时间：
2010-10-28
期刊：
影响因子：
3.7
通讯作者：
Matsuoka H
中科院分区：
文献类型：
--
作者：
Yoshida S;Nagumo H;Yokomine T;Araki H;Suzuki A;Matsuoka H
目前两种主要的恶性疟原虫血液期疫苗候选抗原，裂殖子表面蛋白1(MSP119)的C末端区域(MSP119)和顶膜抗原1(AMA1)已被优先考虑，因为它们在约氏疟原虫啮齿动物模型中取得了突出的保护效果。然而，基于这些抗原的恶性疟原虫疫苗在临床试验中的结果令人失望。在约氏疟原虫模型和人体临床试验中观察到的疫苗效力的差异仍然存在问题。在这项研究中，我们使用伯氏疟原虫及其转基因模型评估了一系列基于MSP119和AMA1的疫苗的保护效果。用表达恶性疟原虫MSP119的杆状病毒疫苗(BBV)免疫小鼠，诱导高滴度的PfMSP119特异性抗体，该抗体与恶性疟原虫血液期寄生虫发生强烈反应。然而，用表达PfMSP119的转基因伯氏假单胞菌代替天然的PbMSP119进行致死攻击后，没有获得保护。同样，无论是MSP119-MSP119-BBV还是AMA1-BBV，对伯氏疫霉都不起作用。相比之下，约氏疟原虫MSP119-和AMA1-BBV对约氏疟原虫致死攻击的保护率分别为100%和40%。对伯氏肺孢子虫自然产生不育免疫的小鼠对约氏肺孢子虫产生交叉抗药性，但反之亦然。这是第一项同时使用伯氏疟原虫和约氏疟原虫模型来解决血液阶段疫苗有效性的研究。伯氏假单胞菌完全绕过了以MSP119和AMA1为基础的疫苗诱导的免疫反应，这表明伯氏假单胞菌拥有额外的分子和/或机制来绕过宿主对MSP119和AMA1的免疫反应，这是约氏假单胞菌所缺乏的。尽管目前尚不清楚恶性疟原虫与伯氏疟原虫是否具有相同的逃逸机制，但伯氏疟原虫及其转基因模型有可能成为鉴定和评估恶性疟原虫新的血液期疫苗候选抗原的有用工具。
Two current leading malaria blood-stage vaccine candidate antigens for Plasmodium falciparum, the C-terminal region of merozoite surface protein 1 (MSP119) and apical membrane antigen 1 (AMA1), have been prioritized because of outstanding protective efficacies achieved in a rodent malaria Plasmodium yoelii model. However, P. falciparum vaccines based on these antigens have had disappointing outcomes in clinical trials. Discrepancies in the vaccine efficacies observed between the P. yoelii model and human clinical trials still remain problematic. In this study, we assessed the protective efficacies of a series of MSP119- and AMA1-based vaccines using the P. berghei rodent malarial parasite and its transgenic models. Immunization of mice with a baculoviral-based vaccine (BBV) expressing P. falciparum MSP119 induced high titers of PfMSP119-specific antibodies that strongly reacted with P. falciparum blood-stage parasites. However, no protection was achieved following lethal challenge with transgenic P. berghei expressing PfMSP119 in place of native PbMSP119. Similarly, neither P. berghei MSP119- nor AMA1-BBV was effective against P. berghei. In contrast, immunization with P. yoelii MSP119- and AMA1-BBVs provided 100% and 40% protection, respectively, against P. yoelii lethal challenge. Mice that naturally acquired sterile immunity against P. berghei became cross-resistant to P. yoelii, but not vice versa. This is the first study to address blood-stage vaccine efficacies using both P. berghei and P. yoelii models at the same time. P. berghei completely circumvents immune responses induced by MSP119- and AMA1-based vaccines, suggesting that P. berghei possesses additional molecules and/or mechanisms that circumvent the host's immune responses to MSP119 and AMA1, which are lacking in P. yoelii. Although it is not known whether P. falciparum shares these escape mechanisms with P. berghei, P. berghei and its transgenic models may have potential as useful tools for identifying and evaluating new blood-stage vaccine candidate antigens for P. falciparum.
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影响因子：
3.7
作者：
Lyon, Jeffrey A.;Angov, Evelina;Barnwell, John W.
通讯作者：
Barnwell, John W.
影响因子：
3.1
作者：
DALY, TM;LONG, CA
通讯作者：
LONG, CA
影响因子：
2.2
作者：
Egan, AF;Burghaus, P;Riley, EM
通讯作者：
Riley, EM
DOI：
10.1084/jem.20030085
发表时间：
2003-09-15
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
de Koning-Ward TF;O'Donnell RA;Drew DR;Thomson R;Speed TP;Crabb BS
通讯作者：
Crabb BS
DOI：
10.1084/jem.172.1.379
发表时间：
1990-07-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Blackman MJ;Heidrich HG;Donachie S;McBride JS;Holder AA
通讯作者：
Holder AA