New adenovirus-based vaccine vectors targeting Pfs25 elicit antibodies that inhibit Plasmodium falciparum transmission.
New adenovirus-based vaccine vectors targeting Pfs25 elicit antibodies that inhibit Plasmodium falciparum transmission.
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DOI：
10.1186/s12936-017-1896-7
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发表时间：
2017-06-15
期刊：
影响因子：
3
通讯作者：
Williamson KC
中科院分区：
文献类型：
--
作者：
McGuire KA;Miura K;Wiethoff CM;Williamson KC
有效的疟疾传播阻断疫苗（TBV）将是目前消除并最终根除疟疾努力的重大进展。已知针对恶性疟原虫表面蛋白Pfs25的抗体可阻断疟原虫在蚊子载体中的发育。然而，在最初的临床试验中，重组Pfs25蛋白佐剂疫苗的有限免疫原性一直是一个挑战。将新型人腺病毒5型（Ad5）载体应用于异源启动增强疫苗接种策略，以增强对Pfs25的免疫应答。具体来说，使用Ad5载体指导全长膜结合Pfs25的表达作为引物免疫，然后用Ad5病毒颗粒增强，该病毒颗粒仅显示由传递阻断抗体4B7和1D2 （Pfs25 aa 122-134）靶向的Pfs25表位，位于六元衣壳蛋白的高变区5。在标准的膜喂养试验中，这种异源的初强化疫苗策略诱导的抗体显著抑制了恶性疟原虫向蚊子的传播。此外，与重组Pfs25/明矾免疫小鼠相比，免疫小鼠产生了强大的抗Pfs25抗体反应，其特征是更高的滴度、更高的相对亲和力和更广泛的IgG亚类谱。这些数据表明，将免疫反应集中在病毒衣壳上显示的特定表位上是一种有效的传播阻断疫苗开发策略。
An effective malaria transmission-blocking vaccine (TBV) would be a major advance in the current efforts to eliminate and, ultimately, eradicate malaria. Antibodies against Plasmodium falciparum surface protein, Pfs25, are known to block parasite development in the mosquito vector. However, in initial clinical trials the limited immunogenicity of recombinant Pfs25 protein-in-adjuvant vaccines has been a challenge. Novel human adenovirus type 5 (Ad5) vectors were used in heterologous prime boost vaccination strategies to augment the immune response against Pfs25. Specifically, an Ad5 vector that directs expression of full-length, membrane-bound Pfs25 was used as a priming immunization followed by a boost with Ad5 viral particles displaying only the Pfs25 epitope targeted by transmission-blocking antibodies 4B7 and 1D2 (Pfs25 aa 122–134) in hypervariable region 5 of the hexon capsid protein. This heterologous prime-boost vaccine strategy induced antibodies that significantly inhibit P. falciparum transmission to mosquitoes in a standard membrane-feeding assay. Further, immunized mice generated a robust anti-Pfs25 antibody response characterized by higher titer, higher relative avidity and a broader IgG subclass profile than observed with a homologous prime-boost with recombinant Pfs25/alum. The data suggest that focusing the immune response against defined epitopes displayed on the viral capsid is an effective strategy for transmission-blocking vaccine development.