间日疟原虫配子融合因子PvHAP2传播阻断效应的评估  

EVALUATION OF TRANSMISSION BLOCKING EFFECT OF GAMETE FUSION FACTOR PVHAP2 IN PLASMODIUM VIVAX

作　　者：刘鹏波 张耀文 赵艳[1] 郁春云 曹雅明[1] LIU Peng-Bo;ZHANG Yao-Wen;ZHAO Yan;YU Chun-Yun;CAO Ya-Ming(Department of Immunology,China Medical University,Shenyang,Liaoning 110122,China)

机构地区：[1]中国医科大学免疫学教研室,辽宁沈阳110122

出　　处：《寄生虫与医学昆虫学报》2021年第1期1-7,13,共8页Acta Parasitologica et Medica Entomologica Sinica

基　　金：国家自然科学基金项目(No.81761128017)。

摘　　要：东南亚大湄公河区域(GMS)内的6个国家批准了2030年前在该地区实现完全消除疟疾的区域性疟疾消除计划,传播阻断疫苗(TBV)作为实现这一计划的有力武器面临着候选抗原数量不足的缺陷。本文研究了配子融合蛋白PvHAP2的传播阻断活性,以评估其作为TBV候选抗原的潜能。通过原核表达系统表达了PvHAP2的HAP2/GCS1结构域从而获得了重组蛋白,并用其免疫BALB/c雌性小鼠获得抗体。通过间接免疫荧光分析显示抗PvHAP2抗体仅与间日疟原虫雄性配子体反应。结果显示,在用临床分离株进行的标准膜饲实验(SMFA)中发现抗PvHAP2抗体能够抑制间日疟原虫卵囊在雌性按蚊宿主体内形成。相比较于对照组,用与抗PvHAP2抗体混合后的间日疟原虫患者血液饲喂按蚊后,按蚊感染率降低25%,平均卵囊数降低15.3%。但抑制效果不如杆状病毒表达蛋白免疫获得的抗血清明显,导致这一情况出现的原因需要进一步探讨。结果表明,HAP2有成为TBV候选抗原的潜质,但相较原核表达蛋白系统更为高效的蛋白表达系统值得深入的研究。Recently,six countries in the Greater Mekong Sub-region(GMS)of Southeast Asia have approved a regional malaria elimination plan to achieve complete malaria eradication by 2030.Transmission blocking vaccine(TBV),as a powerful weapon,is facing with the shortage of candidate antigens.The transmission blocking activity of gamete fusion protein PvHAP2 was studied in present study to evaluate its'possibility as candidate antigen of TBV.The recombinant protein was obtained by expressing the HAP2/GCS1 domain of PvHAP2 via the prokaryotic expression system,and with it antibodies were obtained by immunizing BALB/c female mice.Indirect immunofluorescence analysis showed that the anti-PvHAP2 antibody reacted only with the male gametophyte of Plasmodium vivax.The standard membrane feeding assay(SMFA)with clinical isolates demonstrated that anti-PvHAP2 antibody could inhibit the formation of oocysts in female Anopheles mosquitoes.Compared with the control group,the infection rate reduced by 25% in Anopheles mosquitoes fed with blood from patients with P.vivax mixed with anti-PvHAP2 antibody,and the mean oocyst number reduced by 15.3%.But the inhibitory effect was lower than the antisera obtained from the baculovirus expressed protein immunized mice,the reason led to such situation need to be further studied.The results showed that HAP2 has the potential to be a candidate antigen for TBV,but more efficient protein expression system than the prokaryotic expression system should be used by further study.

关 键 词：间日疟原虫 PvHAP2 配子体 传播阻断疫苗 

分 类 号：R382.31[医药卫生—医学寄生虫学]