Science2014-06-10 2:58 PM

发现可阻断疟原虫复制的天然抗体 Antibodies to PfSEA-1 block parasite egress from RBCs and protect against malaria infection

论文摘要 

科学家们继续在探索候选的疟疾疫苗,尽管他们的努力目前局限于4种疟疾抗原的范围内。尽管需要有新的候选抗原,但发现它们的方法一直是有限的。

Dipak Raj及其同事对坦桑尼亚——疟疾在那里是地方病——的对疟疾有抵抗力的2岁孩子的血浆进行了研究并发现,恶性虐原虫的一种被称作PfSEA-1的特定抗原在这些孩子的体内促发了抗体的产生,并转而阻断了该疟原虫的复制。

当研究人员用该抗原来接种感染疟疾的小鼠或被动地将PfSEA-1抗体转移到小鼠体内,他们随后观察到在这些小鼠血液中的疟原虫减少了4倍。PfSEA-1抗体的存在似乎也能保护坦桑尼亚年幼的研究参与者免得严重的疟疾;当研究人员对肯尼亚的一组独特的儿童和青少年进行分析时,他们发现,PfSEA-1抗体一般也能将病人血液中的疟原虫数减半。这些发现或能让研究人员距离研发出一种有效疟疾疫苗更近了一步,而这种疫苗能以疟原虫多个生命阶段作为标靶。

Abstract 

Novel vaccines are urgently needed to reduce the burden of severe malaria. Using a differential whole-proteome screening method, we identified Plasmodium falciparum schizont egress antigen-1 (PfSEA-1), a 244-kilodalton parasite antigen expressed in schizont-infected red blood cells (RBCs). Antibodies to PfSEA-1 decreased parasite replication by arresting schizont rupture, and conditional disruption of PfSEA-1 resulted in a profound parasite replication defect. Vaccination of mice with recombinant Plasmodium berghei PbSEA-1 significantly reduced parasitemia and delayed mortality after lethal challenge with the Plasmodium berghei strain ANKA. Tanzanian children with antibodies to recombinant PfSEA-1A (rPfSEA-1A) did not experience severe malaria, and Kenyan adolescents and adults with antibodies to rPfSEA-1A had significantly lower parasite densities than individuals without these antibodies. By blocking schizont egress, PfSEA-1 may synergize with other vaccines targeting hepatocyte and RBC invasion.

Editor's Summary

Progress toward an effective malaria vaccine

The history of efforts to develop a malaria vaccine has been long and difficult. Raj et al. probed for molecules produced by this blood parasite that are recognized by natural immune responses of people living in malaria-endemic areas of Africa. One, PfSEA-1, blocked parasite exit from red blood cells. Vaccination experiments with mouse malaria showed almost fourfold reduction in parasitemia; moreover, passive transfer of PfSEA-1 antibodies transferred protection from mouse to mouse. Encouragingly, the presence of PfSEA-1 antibodies correlates with significant protection from severe malaria in children and adolescents from Kenya and Tanzania.

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