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In vivo Characterization of Plasmodium berghei P47 (Pbs47) as a Malaria Transmission-Blocking Vaccine Target.
Frontiers in Microbiology ( IF 5.2 ) Pub Date : 2020-06-08 , DOI: 10.3389/fmicb.2020.01496
Lampouguin Yenkoidiok-Douti 1, 2 , Gaspar E Canepa 1 , Ana Beatriz F Barletta 1 , Carolina Barillas-Mury 1
Affiliation  

An effective vaccine to reduce malaria transmission is central to control and ultimately achieve disease eradication. Recently, we demonstrated that antibodies targeting the Plasmodium falciparum surface protein P47 (Pfs47) reduce parasite transmission to Anopheles gambiae mosquitoes. Here, Plasmodium berghei (Pb) was used as a model to assess the in vivo efficacy of a P47-targeted transmission blocking vaccine (Pbs47). Mice were immunized following a prime/boost regimen and infected with P. berghei. The effect of immunization on infectivity to mosquitoes was evaluated by direct feeding on P. berghei-infected mice. The key region in Pbs47 where antibody binding confers protection was mapped, and the immunogenicity of this protective antigen was enhanced by conjugation to a virus-like particle. Passive immunization with 100 and 50 μg/mL of anti-Pbs47 IgG reduced oocyst density by 77 and 67%, respectively. Furthermore, affinity purified Pbs47-specific IgG significantly reduced oocyst density by 88 and 77%, respectively at doses as low as 10 and 1 μg/mL. These studies suggest that P47 is a promising transmission blocking target and show that antibodies to the same specific region in Pfs47 and Pbs47 confer protection.



中文翻译:

伯氏疟原虫P47(Pbs47)作为疟疾传播阻断疫苗目标的体内表征。

有效减少疟疾传播的疫苗对于控制并最终实现根除疾病至关重要。最近,我们证明了针对恶性疟原虫 表面蛋白P47(Pfs47)减少了寄生虫的传播 冈比亚按蚊蚊子。这里,伯氏疟原虫 (Pb)作为模型评估 体内靶向P47的传播阻断疫苗(Pbs47)的功效。在初免/加强方案下对小鼠进行免疫并感染伯氏疟原虫。通过直接喂食对小鼠的免疫力来评估其对蚊子感染性的影响。伯氏疟原虫感染的小鼠。Pbs47中的抗体结合赋予了保护作用的关键区域被定位,并且该保护性抗原的免疫原性通过与病毒样颗粒的结合而得以增强。用100和50μg/ mL的抗Pbs47 IgG进行的被动免疫分别将卵囊密度降低了77%和67%。此外,亲和纯化的Pbs47特异性IgG在低至10和1μg/ mL的剂量下,卵囊密度分别显着降低了88%和77%。这些研究表明,P47是有希望的传输阻断靶标,并表明针对Pfs47和Pbs47中相同特定区域的抗体具有保护作用。

更新日期:2020-07-03
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