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Vaccination with virosomally formulated recombinant CyRPA elicits protective antibodies against Plasmodium falciparum parasites in preclinical in vitro and in vivo models.
npj Vaccines ( IF 9.2 ) Pub Date : 2020-01-31 , DOI: 10.1038/s41541-020-0158-9
Marco Tamborrini 1, 2 , Julia Hauser 1, 2 , Anja Schäfer 1, 2 , Mario Amacker 3 , Paola Favuzza 1, 2 , Kwak Kyungtak 1, 2 , Sylvain Fleury 3 , Gerd Pluschke 1, 2
Affiliation  

The Plasmodium falciparum (Pf) cysteine-rich protective antigen (PfCyRPA) has emerged as a promising blood-stage candidate antigen for inclusion into a broadly cross-reactive malaria vaccine. This highly conserved protein among various geographical strains plays a key role in the red blood cell invasion process by P. falciparum merozoites, and antibodies against PfCyRPA can efficiently prevent the entry of the malaria parasites into red blood cells. The aim of the present study was to develop a human-compatible formulation of the PfCyRPA vaccine candidate and confirming its activity in preclinical studies. Recombinant PfCyRPA expressed in HEK 293 cells was chemically coupled to phosphoethanolamine and then incorporated into the membrane of unadjuvanted influenza virosomes approved as antigen delivery system for humans. Laboratory animals were immunised with the virosome-based PfCyRPA vaccine to determine its immunogenic properties and in particular, its capacity to elicit parasite binding and growth-inhibitory antibodies. The vaccine elicited in mice and rabbits high titers of PfCyRPA-specific antibodies that bound to the blood-stage parasites. At a concentration of 10 mg/mL, purified total serum IgG from immunised rabbits inhibited parasite growth in vitro by about 80%. Furthermore, in a P. falciparum infection mouse model, passive transfer of 10 mg of purified total IgG from PfCyRPA vaccinated rabbits reduced the in vivo parasite load by 77%. Influenza virosomes thus represent a suitable antigen delivery system for the induction of protective antibodies against the recombinant PfCyRPA, designating it as a highly suitable component for inclusion into a multivalent and multi-stage virosomal malaria vaccine.

中文翻译:

在临床前体外和体内模型中,用病毒体配制的重组 CyRPA 进行疫苗接种会引发针对恶性疟原虫寄生虫的保护性抗体。

恶性疟原虫 (Pf) 富含半胱氨酸的保护性抗原 (PfCyRPA) 已成为一种有前途的血液阶段候选抗原,可纳入广泛交叉反应的疟疾疫苗。这种在不同地理菌株中高度保守的蛋白质在恶性疟原虫裂殖子侵入红细胞的过程中起着关键作用,针对 PfCyRPA 的抗体可以有效阻止疟原虫进入红细胞。本研究的目的是开发一种与人体相容的 PfCyRPA 候选疫苗制剂,并在临床前研究中确认其活性。在 HEK 293 细胞中表达的重组 PfCyRPA 与磷酸乙醇胺化学偶联,然后掺入被批准用作人类抗原传递系统的无佐剂流感病毒体的膜中。用基于病毒体的 PfCyRPA 疫苗对实验室动物进行免疫,以确定其免疫原性,特别是其引发寄生虫结合和生长抑制抗体的能力。该疫苗在小鼠和兔子中引发了与血液阶段寄生虫结合的高滴度 PfCyRPA 特异性抗体。在 10 mg/mL 的浓度下,来自免疫兔的纯化总血清 IgG 在体外抑制寄生虫生长约 80%。此外,在恶性疟原虫感染小鼠模型中,从接种 PfCyRPA 的兔子中被动转移 10 mg 纯化的总 IgG 将体内寄生虫负荷降低了 77%。因此,流感病毒体代表了一种合适的抗原递送系统,用于诱导针对重组 PfCyRPA 的保护性抗体,
更新日期:2020-01-31
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