Nasal immunization with a malaria transmission-blocking vaccine candidate, Pfs25, induces complete protective immunity in mice against field isolates of Plasmodium falciparum
Nasal immunization with a malaria transmission-blocking vaccine candidate, Pfs25, induces complete protective immunity in mice against field isolates of Plasmodium falciparum
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DOI：
10.1128/iai.73.11.7375-7380.2005
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发表时间：
2005-11-01
影响因子：
3.1
通讯作者：
Tsuboi, T
中科院分区：
文献类型：
--
作者：
Arakawa, T;Komesu, A;Tsuboi, T
疟疾传播阻断疫苗的基础上表达的抗原性阶段的寄生虫被认为是一个有前途的战略疟疾控制。为探讨恶性疟原虫非侵入性粘膜传播阻断疫苗的可行性，采用毕赤酵母表达的重组Pfs 25蛋白进行鼻内免疫实验。小鼠鼻内免疫的Pfs 25蛋白在一个有效的粘膜佐剂霍乱毒素的存在下诱导强大的全身以及粘膜抗体。所有小鼠免疫球蛋白G（IgG）亚类，除了IgG3在血清中发现在相当的水平，这表明免疫诱导混合Th1和Th2的反应。与寄生虫中Pfs 25蛋白的表达模式一致，诱导的免疫血清特异性地识别动合子，但不识别配子体。此外，免疫血清识别Pfs 25蛋白的天然构象，但不是变性形式，表明粘膜免疫诱导的生物活性抗体能够识别天然Pfs 25蛋白的构象表位。用小鼠免疫血清和来自感染恶性疟原虫的患者的配子血的混合物喂养大劣按蚊，导致完全干扰蚊子中肠中的卵囊发育。所观察到的传播阻断活动与特异性血清抗体滴度密切相关。我们的研究结果首次证明了恶性疟原虫传播阻断疫苗候选物对现场分离的寄生虫是有效的，并且可以证明用于控制疟疾的非侵入性粘膜接种方案的研究是合理的，它是典型的粘膜无关的蚊媒寄生虫病。
Malaria transmission-blocking vaccines based on antigens expressed in sexual stages of the parasites are considered one promising strategy for malaria control. To investigate the feasibility of developing noninvasive mucosal transmission-blocking vaccines against Plasmodium falciparum, intranasal immunization experiments with Pichia pastoris-expressed recombinant Pfs25 proteins were conducted. Mice intranasally immunized with the Pfs25 proteins in the presence of a potent mucosal adjuvant cholera toxin induced robust systemic as well as mucosal antibodies. All mouse immunoglobulin G (IgG) subclasses except IgG3 were found in serum at comparable levels, suggesting that the immunization induced mixed Th1 and Th2 responses. Consistent with the expression patterns of the Pfs25 proteins in the parasites, the induced immune sera specifically recognized ookinetes but not gametocytes. In addition, the immune sera recognized Pfs25 proteins with the native conformation but not the denatured forms, indicating that mucosal immunization induced biologically active antibodies capable of recognizing conformational epitopes of native Pfs25 proteins. Feeding Anopheles dirus mosquitoes with a mixture of the mouse immune sera and gametocytemic blood derived from patients infected with P. falciparum resulted in complete interference with oocyst development in mosquito midguts. The observed transmission-blocking activities were strongly correlated with specific serum antibody titers. Our results demonstrated for the first time that a P. falciparum transmission-blocking vaccine candidate is effective against field-isolated parasites and may justify the investigation of noninvasive mucosal vaccination regimens for control of malaria, it prototypical mucosa-unrelated mosquito-borne parasitic disease.