Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland, USA.
The EMMES Corporation, Rockville, Maryland, USA.
mSphere. 2019 Mar 20;4(2):e00097-19. doi: 10.1128/mSphere.00097-19.
The repetitive interspersed family (RIFIN) and the subtelomeric variable open reading frame (STEVOR) family represent two of three major 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. Malaria, an infectious disease caused by the parasite , 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.
重复插入家族（RIFIN）和端粒可变开放阅读框（STEVOR）家族代表了三种主要的变异表面抗原家族中的两种，它们与疟疾发病机制和免疫逃避有关，是天然免疫发展的潜在目标。用与马里儿童严重疟疾易感性相关的 RIFIN 和 STEVOR 蛋白和肽微阵列探测成人和儿科血清，以鉴定反映疟疾暴露的表位。成人血清对所有 STEVOR 蛋白的识别和反应强度均高于儿科血清。随着年龄的增长和季节性疟疾暴露，STE-VOR 半保守结构域内肽的血清识别和反应性增加，而 RIFIN 的半保守和第二超变结构域的血清识别和反应性仅随年龄增加而增加。在半保守结构域内针对 RIFIN 和 STEVOR 肽的血清反应可能在对严重疟疾的天然免疫中发挥作用。疟疾是一种由寄生虫引起的传染病，每年在全球造成近 43.5 万人死亡。RIFIN 和 STEVOR 是两种参与疟疾发病机制和免疫逃避的变异表面抗原家族。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。这是第一项比较疟疾流行地区儿童和成人对 RIFIN 和 STEVOR 的血清反应，并在临床疟疾发作前后检查这些血清反应的研究。我们使用微阵列确定了这两种寄生虫变异表面抗原家族中的半保守结构域中存在其血清反应性反映疟疾暴露的肽。类似的方法有可能阐明变异表面抗原在临床疟疾天然免疫发展中的作用。严重疟疾的潜在疫苗应考虑包括 RIFIN 和 STEVOR 的半保守结构域内的肽。
