Arakawa Takeshi, Tsuboi Takafumi, Kishimoto Ayano, Sattabongkot Jetsumon, Suwanabun Nantavadee, Rungruang Thanaporn, Matsumoto Yasunobu, Tsuji Naotoshi, Hisaeda Hajime, Stowers Anthony, Shimabukuro Isao, Sato Yoshiya, Torii Motomi
Division of Molecular Microbiology, Center of Molecular Biosciences, University of the Ryukyus, Nishihara, 903-0213, Okinawa, Japan.
Vaccine. 2003 Jul 4;21(23):3143-8. doi: 10.1016/s0264-410x(03)00258-5.
Transmission-blocking vaccines (TBVs) targeting ookinete surface proteins expressed on sexual-stage malaria parasites are considered one promising strategy for malaria control. To evaluate the prospect of developing non-invasive and easy-to-administer mucosal malaria transmission-blocking vaccines, mice were immunized intranasally with a Plasmodium vivax ookinete surface protein, Pvs25 with a mucosal adjuvant cholera toxin (CT). Immunization induced significant serum IgG with high IgG1/IgG2a ratio (indicative of Th-2 type immune response). Feeding Anopheles dirus mosquitoes with mixtures of immune sera and gametocytemic blood derived from vivax-infected volunteer patients in Thailand significantly reduced both the number of midgut oocysts as well as the percentage of infected mosquitoes. The observed transmission-blocking effect was dependent on immune sera dilution. This study demonstrates for the first time that the mucosally induced mouse immune sera against a human malaria ookinete surface protein can completely block parasite transmission to vector mosquitoes, suggesting the possibility of non-invasive mucosal vaccines against mucosa-unrelated important pathogens like malaria.
针对有性期疟原虫表达的动合子表面蛋白的传播阻断疫苗(TBVs)被认为是疟疾控制的一种有前景的策略。为了评估开发非侵入性且易于给药的黏膜疟疾传播阻断疫苗的前景,用间日疟原虫动合子表面蛋白Pvs25与黏膜佐剂霍乱毒素(CT)经鼻内免疫小鼠。免疫诱导出显著的血清IgG,IgG1/IgG2a比值较高(表明是Th-2型免疫反应)。用来自泰国间日疟感染志愿者患者的免疫血清和配子体血症血液的混合物喂养大劣按蚊,显著减少了中肠卵囊的数量以及受感染蚊子的百分比。观察到的传播阻断效果取决于免疫血清的稀释度。本研究首次证明,经黏膜诱导产生的针对人类疟疾动合子表面蛋白的小鼠免疫血清可完全阻断寄生虫向媒介蚊子的传播,这表明有可能开发针对疟疾等与黏膜无关的重要病原体的非侵入性黏膜疫苗。