Abstract:
Plasmodium vivax serological exposure markers (SEMs) have emerged as promising tools for the actionable surveillance and implementation of targeted interventions to accelerate malaria elimination. To determine the dynamic profiles of SEMs in current and past P. vivax infections, we screened and selected 11 P. vivax proteins from 210 putative proteins using protein arrays, with a set of serum samples obtained from patients with acute P. vivax and documented past P. vivax infections. Then we used a murine protein immune model to initially investigate the humoral and memory B cell response involved in the generation of long-lived antibodies. We show that of the 11 proteins, especially C-terminal 42-kDa region of P. vivax merozoite surface protein 1 (PvMSP1-42) induced longer-lasting long-lived antibodies, as these antibodies were detected in individuals infected with P. vivax in the 1960-1970s who were not re-infected until 2012. In addition, we provide a potential mechanism for the maintenance of long-lived antibodies after the induction of PvMSP1-42. The results indicate that PvMSP1-42 induces more CD73+CD80+ memory B cells (MBCs) compared to P. vivax GPI-anchored micronemal antigen (PvGAMA), allowing IgG anti-PvMSP1-42 antibodies to be maintained for a long time.
摘要:
间日疟原虫血清学暴露标志物(SEM)已成为可行的监测和实施针对性干预措施以加速消除疟疾的有希望的工具。为了确定当前和过去间日疟原虫感染中SEM的动态概况,我们使用蛋白质阵列从210种推定的蛋白质中筛选并选择了11种间日疟原虫蛋白质,从急性间日疟原虫患者获得的一组血清样本,并记录了过去的间日疟原虫感染。然后,我们使用鼠蛋白质免疫模型来初步研究涉及长寿命抗体产生的体液和记忆B细胞反应。我们发现在这11种蛋白质中,特别是间日疟原虫裂殖子表面蛋白1(PvMSP1-42)的C端42-kDa区域诱导了更持久的长寿命抗体,因为这些抗体是在1960-1970年代间日疟原虫感染的个体中检测到的,这些个体直到2012年才重新感染。此外,我们提供了在诱导PvMSP1-42后维持长寿命抗体的潜在机制。结果表明,与间日疟原虫GPI锚定的微丝抗原(PvGAMA)相比,PvMSP1-42诱导更多的CD73CD80记忆B细胞(MBC),允许IgG抗PvMSP1-42抗体长时间维持。