Adenovirus-vectored Plasmodium vivax ookinete surface protein, Pvs25, as a potential transmission-blocking vaccine.
Adenovirus-vectored Plasmodium vivax ookinete surface protein, Pvs25, as a potential transmission-blocking vaccine.
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DOI：
10.1016/j.vaccine.2011.01.083
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发表时间：
2011-03
期刊：
影响因子：
5.5
通讯作者：
T. Miyata;T. Harakuni;H. Sugawa;J. Sattabongkot;Aki Kato;M. Tachibana;M. Torii;T. Tsuboi;T. Arakawa
中科院分区：
文献类型：
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作者：
T. Miyata;T. Harakuni;H. Sugawa;J. Sattabongkot;Aki Kato;M. Tachibana;M. Torii;T. Tsuboi;T. Arakawa
佐剂或运载工具是加快疟疾疫苗开发的重要组成部分。在本研究中，复制缺陷人腺病毒血清型5型(Rad)被转基因表达间日疟原虫运动表面蛋白(OSP)Pvs25(AdPvs25)。用AdPvs25通过不同途径免疫BALB/c小鼠，包括肌肉、皮下和鼻腔途径，以诱导抗原特异性传播阻断免疫。肠外免疫，但不是粘膜免疫，可诱导针对从泰国间日疟原虫志愿者患者中分离的间日疟原虫的高血清免疫球蛋白G(IgG)反应。膜饲喂试验表明，抗血清可使平均每只蚊子的卵囊数减少99%，而表达Pfs25的恶性疟原虫Rad免疫只产生背景水平的阻断，提示诱导了一种物种特异性的传播阻断免疫。AdPvs25的疫苗效力略高于与氢氧化铝混合的重组Pvs25蛋白，但低于用不完全弗氏佐剂乳化的蛋白。这项研究是首次对腺病毒载体的疟疾OSP进行临床前评估，暗示病毒载体系统中可能包括疟疾传播阻断疫苗抗原。
Adjuvants or delivery vehicles are essential components to expedite malaria vaccine development. In this study, replication-defective human adenovirus serotype 5 (rAd) was genetically engineered to express the Plasmodium vivax ookinete surface protein (OSP), Pvs25 (AdPvs25). BALB/c mice immunized with the AdPvs25 through various routes including intramuscular, subcutaneous and intranasal routes were analyzed for induction of antigen-specific transmission-blocking immunity. Parenteral but not mucosal immunization induced high serum immunoglobulin G (IgG) responses specific to P. vivax ookinetes isolated from P. vivax volunteer patients from Thailand. The membrane feeding assay revealed that antisera conferred a transmission blockade of up to 99% reduction in the average oocyst numbers per mosquito, while immunization with a rAd expressing Pfs25 from Plasmodium falciparum, a homolog of Pvs25, conferred only a background level of blockade, suggesting that a species-specific transmission-blocking immunity was induced. Vaccine efficacy of AdPvs25 was slightly higher than to a recombinant Pvs25 protein mixed with aluminum hydroxide, but less efficacious than the protein emulsified with incomplete Freund's adjuvant. This study, the first preclinical evaluation of adenovirus-vectored malaria OSPs, implicates a potential inclusion of malaria transmission-blocking vaccine antigens in viral vector systems.