McGuire Kathleen A, Miura Kazutoyo, Wiethoff Christopher M, Williamson Kim C
Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, 60153, USA.
Abbvie, 1 North Waukegan Road, North Chicago, IL, 60064, USA.
Malar J. 2017 Jun 15;16(1):254. doi: 10.1186/s12936-017-1896-7.
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.
一种有效的疟疾传播阻断疫苗（TBV）将是当前消除乃至最终根除疟疾努力中的一项重大进展。已知针对恶性疟原虫表面蛋白Pfs25的抗体可阻断寄生虫在蚊媒中的发育。然而，在最初的临床试验中，重组Pfs25蛋白佐剂疫苗的免疫原性有限，这一直是一个挑战。
新型人5型腺病毒（Ad5）载体用于异源初免 - 加强疫苗接种策略，以增强针对Pfs25的免疫反应。具体而言，一种指导全长膜结合Pfs25表达的Ad5载体用作初免，随后用仅展示六邻体衣壳蛋白高变区5中被传播阻断抗体4B7和1D2靶向的Pfs25表位（Pfs25 aa 122 - 134）的Ad5病毒颗粒进行加强免疫。
这种异源初免 - 加强疫苗策略诱导产生的抗体在标准膜饲试验中能显著抑制恶性疟原虫向蚊子的传播。此外，与用重组Pfs25/明矾进行同源初免 - 加强相比，免疫小鼠产生了强烈的抗Pfs25抗体反应，其特征为更高的滴度、更高的相对亲和力和更广泛的IgG亚类谱。
数据表明，针对病毒衣壳上特定表位聚焦免疫反应是开发传播阻断疫苗的有效策略。
