A new rodent model to assess blood stage immunity to the Plasmodium falciparum antigen merozoite surface protein 119 reveals a protective role for invasion inhibitory antibodies.
A new rodent model to assess blood stage immunity to the Plasmodium falciparum antigen merozoite surface protein 119 reveals a protective role for invasion inhibitory antibodies.
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DOI：
10.1084/jem.20030085
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发表时间：
2003-09-15
期刊：
影响因子：
--
通讯作者：
Crabb BS
中科院分区：
文献类型：
--
作者：
de Koning-Ward TF;O'Donnell RA;Drew DR;Thomson R;Speed TP;Crabb BS
能够抑制疟原虫裂殖子侵入红细胞的抗体存在于临床上对疟疾寄生虫免疫的个体中。那些靶向主要裂殖子表面蛋白 (MSP)-119 的 19-kD COOH 末端结构域的药物是这种抑制活性的主要组成部分。然而，很难评估此类抗体与抗寄生虫免疫的总体相关性。在这里，我们使用等位基因替换方法来生成啮齿动物疟疾寄生虫（伯氏疟原虫），它表达人类疟疾（恶性疟原虫）形式的 MSP-119。我们发现，对这种寄生虫系进行半免疫的小鼠会产生高水平的裂殖子抑制抗体，这些抗体对恶性疟原虫 MSP-119 具有特异性。重要的是，这些小鼠免受同源血液阶段攻击的保护与恶性疟原虫 MSP-119 特异性抑制抗体的水平相关，但与 MSP-119 特异性免疫球蛋白总滴度无关。我们的结论是，响应感染而产生的裂殖子抑制抗体在抑制体内寄生虫血症方面可以发挥重要作用。这项研究为开发旨在产生侵袭抑制抗体的血期疫苗提供了强大的推动力，并为试验恶性疟原虫MSP-119疫苗提供了新的动物模型。
Antibodies capable of inhibiting the invasion of Plasmodium merozoites into erythrocytes are present in individuals that are clinically immune to the malaria parasite. Those targeting the 19-kD COOH-terminal domain of the major merozoite surface protein (MSP)-119 are a major component of this inhibitory activity. However, it has been difficult to assess the overall relevance of such antibodies to antiparasite immunity. Here we use an allelic replacement approach to generate a rodent malaria parasite (Plasmodium berghei) that expresses a human malaria (Plasmodium falciparum) form of MSP-119. We show that mice made semi-immune to this parasite line generate high levels of merozoite inhibitory antibodies that are specific for P. falciparum MSP-119. Importantly, protection from homologous blood stage challenge in these mice correlated with levels of P. falciparum MSP-119–specific inhibitory antibodies, but not with titres of total MSP-119–specific immunoglobulins. We conclude that merozoite inhibitory antibodies generated in response to infection can play a significant role in suppressing parasitemia in vivo. This study provides a strong impetus for the development of blood stage vaccines designed to generate invasion inhibitory antibodies and offers a new animal model to trial P. falciparum MSP-119 vaccines.
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影响因子：
15.3
作者：
O'Donnell, R A;de Koning-Ward, T F;Burt, R A;Bockarie, M;Reeder, J C;Cowman, A F;Crabb, B S
通讯作者：
Crabb, B S
DOI：
10.1084/jem.186.10.1689
发表时间：
1997-11-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Guevara Patiño JA;Holder AA;McBride JS;Blackman MJ
通讯作者：
Blackman MJ
影响因子：
2.2
作者：
Egan, AF;Burghaus, P;Riley, EM
通讯作者：
Riley, EM
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
影响因子：
1.5
作者：
COOPER, JA;COOPER, LT;SAUL, AJ
通讯作者：
SAUL, AJ