Antibodies to Peptides in Semiconserved Domains of RIFINs and STEVORs Correlate with Malaria Exposure
Antibodies to Peptides in Semiconserved Domains of RIFINs and STEVORs Correlate with Malaria Exposure
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DOI：
10.1128/msphere.00097-19
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发表时间：
2019-03-01
期刊：
影响因子：
4.8
通讯作者：
Travassos, Mark A.
中科院分区：
文献类型：
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作者：
Zhou, Albert E.;Berry, Andrea A.;Travassos, Mark A.
重复散布家族(RIFIN)和亚端粒可变开放阅读框架(STEVOR)家族代表了恶性疟原虫三个主要表面抗原家族中的两个，参与了疟疾的发病和免疫逃避，是自然免疫发展的潜在靶点。用成人和儿童血清对填充了与马里儿童严重疟疾易感性相关的RIFIN和STEVOR的蛋白质和多肽微阵列进行了探测，以确定反映疟疾暴露的表位。成人血清对所有STEVOR蛋白的识别和反应比儿童血清更强。随着年龄和季节性疟疾暴露，STEVORs半服务结构域内的多肽的血清识别和血清反应性增加，而RIFINs的半服务和第二高变域的血清识别和血清反应性仅随年龄增加。RIFIN和STEVOR多肽在半服务区的血清学反应可能在严重疟疾的自然免疫中发挥作用。疟疾是由寄生虫恶性疟原虫引起的一种传染病，每年在全球范围内造成近43.5万人死亡。RIFINs和STEVORs是两个变异的表面抗原家族，与疟疾的发病机制和免疫逃避有关。最近的研究表明，缺乏对这些蛋白质的体液免疫与马里儿童的严重疟疾易感性有关。这是首次在疟疾流行环境中比较儿童和成人对RIFIN和STEVOR的血清学反应，并检查临床疟疾发病前后的这种血清学反应。利用芯片，我们确定了这两个寄生虫变异表面抗原家族的半服务区含有多肽，其血清反应性反映了疟疾的暴露。一种类似的方法有可能阐明不同的表面抗原在对临床疟疾的自然免疫发展中的作用。针对严重疟疾的潜在疫苗应包括考虑RIFIN和STEVOR半服务区内的多肽。
The repetitive interspersed family (RIFIN) and the subtelomeric variable open reading frame (STEVOR) family represent two of three major Plasmodium falciparum variant surface antigen families involved in malaria pathogenesis and immune evasion and are potential targets in the development of natural immunity. Protein and peptide microarrays populated with RIFINs and STEVORs associated with severe malaria vulnerability in Malian children were probed with adult and pediatric sera to identify epitopes that reflect malaria exposure. Adult sera recognized and reacted with greater intensity to all STEVOR proteins than pediatric sera did. Serorecognition of and seroreactivity to peptides within the semiconserved domain of STEVORs increased with age and seasonal malaria exposure, while serorecognition and seroreactivity increased for the semiconserved and second hypervariable domains of RIFINs only with age. Serologic responses to RIFIN and STEVOR peptides within the semiconserved domains may play a role in natural immunity to severe malaria.IMPORTANCE Malaria, an infectious disease caused by the parasite Plasmodium falciparum, causes nearly 435,000 deaths annually worldwide. RIFINs and STEVORs are two variant surface antigen families that are involved in malaria pathogenesis and immune evasion. Recent work has shown that a lack of humoral immunity to these proteins is associated with severe malaria vulnerability in Malian children. This is the first study to have compared serologic responses of children and adults to RIFINs and STEVORs in settings of malaria endemicity and to examine such serologic responses before and after a clinical malaria episode. Using microarrays, we determined that the semiconserved domains in these two parasite variant surface antigen families harbor peptides whose seroreactivity reflects malaria exposure. A similar approach has the potential to illuminate the role of variant surface antigens in the development of natural immunity to clinical malaria. Potential vaccines for severe malaria should include consideration of peptides within the semiconserved domains of RIFINs and STEVORs.