Antibodies that inhibit malaria merozoite surface protein-1 processing and erythrocyte invasion are blocked by naturally acquired human antibodies.
Antibodies that inhibit malaria merozoite surface protein-1 processing and erythrocyte invasion are blocked by naturally acquired human antibodies.
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DOI：
10.1084/jem.186.10.1689
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发表时间：
1997-11-17
期刊：
影响因子：
--
通讯作者：
Blackman MJ
中科院分区：
文献类型：
--
作者：
Guevara Patiño JA;Holder AA;McBride JS;Blackman MJ
人恶性疟原虫裂殖子表面蛋白-1（MSP-1）在裂殖子成熟和释放以及红细胞侵入期间经历至少两次内切蛋白水解切割事件。我们以前已经证明，单克隆抗体，抑制红细胞侵入和特异性的表位内的膜近端，COOH末端结构域的MSP-1（MSP-119）防止关键的二级加工步骤，发生在表面上的细胞外裂殖子在红细胞侵入的时间左右。某些其他抗MSP-119 mAb本身既不抑制红细胞侵入也不抑制MSP-1二级加工，其阻断第一组抗体的加工抑制活性，并被称为阻断抗体。我们现在已经直接定量了抗体介导的MSP-1二级加工和侵袭的抑制，以及阻断抗体对此的影响。我们表明，阻断抗体的功能，通过竞争与加工抑制抗体的结合，他们的裂殖子上的表位。对MSP-119之外的某些MSP-1序列具有特异性的多克隆兔抗体也可用作阻断抗体。最重要的是，亲和纯化的天然获得的对MSP-1的NH 2末端83-kD结构域内的表位具有特异性的人抗体非常有效地阻断抗MSP-119 mAb 12.8的加工抑制活性。这些封闭抗体的存在也完全消除了mAb 12.8对体外寄生虫侵入红细胞的抑制作用。因此，阻断抗体（a）是人对疟疾感染的应答的一部分;（B）可以由与加工抑制性抗体的MSP-119靶标无关的MSP-1结构诱导;和（c）具有消除由抗MSP-119抗体介导的保护的潜力。我们的研究结果表明，一个有效的MSP-119为基础的恶性疟疾疫苗的目标应该是诱导抗体反应，防止MSP-1的裂殖子表面的加工。
Merozoite surface protein–1 (MSP-1) of the human malaria parasite Plasmodium falciparum undergoes at least two endoproteolytic cleavage events during merozoite maturation and release, and erythrocyte invasion. We have previously demonstrated that mAbs which inhibit erythrocyte invasion and are specific for epitopes within a membrane-proximal, COOH-terminal domain of MSP-1 (MSP-119) prevent the critical secondary processing step which occurs on the surface of the extracellular merozoite at around the time of erythrocyte invasion. Certain other anti–MSP-119 mAbs, which themselves inhibit neither erythrocyte invasion nor MSP-1 secondary processing, block the processing-inhibitory activity of the first group of antibodies and are termed blocking antibodies. We have now directly quantitated antibody-mediated inhibition of MSP-1 secondary processing and invasion, and the effects on this of blocking antibodies. We show that blocking antibodies function by competing with the binding of processing-inhibitory antibodies to their epitopes on the merozoite. Polyclonal rabbit antibodies specific for certain MSP-1 sequences outside of MSP-119 also act as blocking antibodies. Most significantly, affinity-purified, naturally acquired human antibodies specific for epitopes within the NH2-terminal 83-kD domain of MSP-1 very effectively block the processing-inhibitory activity of the anti-MSP-119 mAb 12.8. The presence of these blocking antibodies also completely abrogates the inhibitory effect of mAb 12.8 on erythrocyte invasion by the parasite in vitro. Blocking antibodies therefore (a) are part of the human response to malarial infection; (b) can be induced by MSP-1 structures unrelated to the MSP-119 target of processing-inhibitory antibodies; and (c) have the potential to abolish protection mediated by anti–MSP-119 antibodies. Our results suggest that an effective MSP-119–based falciparum malaria vaccine should aim to induce an antibody response that prevents MSP-1 processing on the merozoite surface.
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影响因子：
1.5
作者：
CHAPPEL, JA;HOLDER, AA
通讯作者：
HOLDER, AA
影响因子：
6.4
作者：
Egan, AF;Morris, J;Riley, EM
通讯作者：
Riley, EM
影响因子：
3.1
作者：
DALY, TM;LONG, CA
通讯作者：
LONG, CA
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