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Evaluation of Plasmodium vivax HAP2 as a transmission-blocking vaccine candidate

机译：评估疟原虫HAP2作为传输阻塞疫苗候选者

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Transmission-blocking vaccine (TBV) is a promising strategy to interfere with the transmission of malaria. To date, only limited TBV candidate antigens have been identified for Plasmodium vivax. HAP2 is a gamete membrane fusion protein, with homology to the class II viral fusion proteins. Herein we reported the characterization of the PvHAP2 for its potential as a TBV candidate for P. vivax. The HAP2/GCS1 domain of PvHAP2 was expressed in the baculovirus expression system and the recombinant protein was used to raise antibodies in rabbits. Indirect immunofluorescence assays showed that anti-PvHAP2 antibodies reacted only with the male gametocytes on blood smears. Direct membrane feeding assays were conducted using four field P. vivax isolates in Anopheles dirus. At a mean infection intensity of 72.4, 70.7, 51.3, and 15.6 oocysts/midgut with the control antibodies, anti-PvHAP2 antibodies significantly reduced the midgut oocyst intensity by 40.3, 44.4, 61.9, and 89.7%. Whereas the anti-PvHAP2 antibodies were not effective in reducing the infection prevalence at higher parasite exposure (51.3-72.4 oocysts/midgut in the control group), the anti-PvHAP2 antibodies reduced infection prevalence by 50% at a low challenge (15.6 oocysts/midgut). Multiple sequence alignment showed 100% identity among these Thai P. vivax isolates, suggesting that polymorphism may not be an impediment for the utilization of PvHAP2 as a TBV antigen. In conclusion, our results suggest that PvHAP2 could serve as a TBV candidate for P. vivax, and further optimization and evaluation are warranted. (C) 2020 The Author(s). Published by Elsevier Ltd.
机译：传输阻塞疫苗（TBV）是干扰疟疾传播的有希望的策略。迄今为止，已经仅鉴定了有限的TBV候选抗原用于疟原虫vivax。 HAP2是一种配子膜融合蛋白，与II类病毒融合蛋白同源性。在此，我们报道了PVHAP2的表征，其潜在作为P.Vivax的TBV候选。 PVHAP2的HAP2 / GCS1结构域在杆状病毒表达系统中表达，并使用重组蛋白在兔中提高抗体。间接免疫荧光测定显示，抗PVHAP2抗体仅与血液涂片上的雄性配子织物反应。使用四个田间P. vivax分离物进行直接膜进料测定。在平均感染强度为72.4,70.7,51.3和15.6个卵囊/中小肠与对照抗体，抗PVHAP2抗体显着降低了40.3,44.4,61.9和89.7％的中肠卵囊强度。虽然抗PVHAP2抗体在降低较高寄生虫暴露的感染患病率（51.3-72.4卵囊/中肠道中的对照组中），但抗PVHAP2抗体在低挑战（15.6卵囊/）下减少50％的感染患病率中肠）。在这些泰国P.Vivax分离株中显示多个序列比对显示100％的同一性，表明多态性可能不是用于利用PVHAP2作为TBV抗原的障碍。总之，我们的研究结果表明，PVHAP2可以作为P.Vivax的TBV候选者，并保证进一步的优化和评估。 （c）2020提交人。 elsevier有限公司出版

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