Transmission blocking potency and immunogenicity of a plant-produced Pvs25-based subunit vaccine against Plasmodium vivax.
Transmission blocking potency and immunogenicity of a plant-produced Pvs25-based subunit vaccine against Plasmodium vivax.
复制标题
DOI：
10.1016/j.vaccine.2016.05.007
复制
发表时间：
2016-06-14
期刊：
影响因子：
5.5
通讯作者：
Yusibov V
中科院分区：
文献类型：
--
作者：
Blagborough AM;Musiychuk K;Bi H;Jones RM;Chichester JA;Streatfield S;Sala KA;Zakutansky SE;Upton LM;Sinden RE;Brian I;Biswas S;Sattabonkot J;Yusibov V
针对疟原虫性期表达蛋白的疟疾传播阻断（TB）疫苗（TBVs）是减少传播的潜在有效手段。由TBV诱导的抗体阻断蚊子中的寄生虫发育，从而抑制传播到其他人类宿主。动合子表面蛋白P25是TBV发展的主要靶标。最近，使用杂合病毒载体在植物中瞬时表达已被证明是具有成本效益和可规模化生产重组疫苗的策略。利用基于植物病毒的表达系统，我们在本氏烟草中产生了与修饰的地衣多糖酶载体蛋白融合的间日疟原虫P25蛋白（Pvs 25）。在转基因啮齿动物模型中使用多种佐剂纯化、表征并评价该候选疫苗Pvs 25-FhCMB的免疫原性和功效。使用Abisco-100佐剂观察到强度降低高达65%和患病率降低54%的体内TB效果。该免疫原诱导TB应答的能力另外与用表达Pvs 25的病毒载体的异源初免-加强疫苗接种组合。当结合两种平台时观察到显著的阻断，强度和患病率分别降低74%和68%。通过对田间间日疟原虫样本进行直接膜喂养证实了这一观察结果，导致强度/患病率降低85.3%和25.5%。这些数据证明了这种候选疫苗的潜力，并支持在基于植物的系统中表达疟原虫抗原以生产TBV的可行性，同时证明了组合多种疫苗递送系统以最大化功效的潜在优势。
Malaria transmission blocking (TB) vaccines (TBVs) directed against proteins expressed on the sexual stages of Plasmodium parasites are a potentially effective means to reduce transmission. Antibodies induced by TBVs block parasite development in the mosquito, and thus inhibit transmission to further human hosts. The ookinete surface protein P25 is a primary target for TBV development. Recently, transient expression in plants using hybrid viral vectors has demonstrated potential as a strategy for cost-effective and scalable production of recombinant vaccines. Using a plant virus-based expression system, we produced recombinant P25 protein of Plasmodium vivax (Pvs25) in Nicotiana benthamiana fused to a modified lichenase carrier protein. This candidate vaccine, Pvs25-FhCMB, was purified, characterized and evaluated for immunogenicity and efficacy using multiple adjuvants in a transgenic rodent model. An in vivo TB effect of up to a 65% reduction in intensity and 54% reduction in prevalence was observed using Abisco-100 adjuvant. The ability of this immunogen to induce a TB response was additionally combined with heterologous prime-boost vaccination with viral vectors expressing Pvs25. Significant blockade was observed when combining both platforms, achieving a 74% and 68% reduction in intensity and prevalence, respectively. This observation was confirmed by direct membrane feeding on field P. vivax samples, resulting in reductions in intensity/prevalence of 85.3% and 25.5%. These data demonstrate the potential of this vaccine candidate and support the feasibility of expressing Plasmodium antigens in a plant-based system for the production of TBVs, while demonstrating the potential advantages of combining multiple vaccine delivery systems to maximize efficacy.