Whole-Killed Blood-Stage Vaccine-Induced Immunity Suppresses the Development of Malaria Parasites in Mosquitoes

Whole-Killed Blood-Stage Vaccine-Induced Immunity Suppresses the Development of Malaria Parasites in Mosquitoes
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全灭活血期疫苗诱导的免疫抑制蚊子体内疟疾寄生虫的发育

DOI:
10.4049/jimmunol.1600979
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发表时间:
2017-01
期刊:
J Immunol
影响因子:
--
通讯作者:
Wenyue Xu
Wenyue Xu
中科院分区:
其他
文献类型:
--
作者:
Chenghao Zhao;Xiao Lu;Jian Zhang;Wenyue Xu

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由于阻断疟疾传播的疫苗本身并不能给接受者带来直接的好处,因此有必要开发一种不仅能阻断疟疾传播,而且能保护接种疫苗的个人的疫苗。在这项研究中,我们观察到,全灭活血液阶段疫苗(WKV)不仅提供保护,对血液阶段的挑战,但也显着抑制不同菌株的疟疾寄生虫的传播。虽然在用疟原虫攻击的WKV免疫小鼠中寄生虫血症低得多,但在感染的早期阶段,对照和免疫小鼠之间的配子体血症是相当的。在将寄生虫过继转移到WKV免疫的小鼠中之前耗尽CD 4 + T细胞对蚊子中疟原虫的发育没有影响,但是将来自免疫的小鼠的血清过继转移到寄生虫接种的小鼠中显著抑制蚊子中疟原虫的发育。此外,用疟疾寄生虫攻击的免疫小鼠产生更高水平的寄生虫特异性Ab和炎性细胞因子MCP-1和IFN-γ。然而,寄生虫特异性IgG的过继转移或MCP-1而非IFN-γ的耗竭在一定程度上与疟原虫在蚊子中发育的抑制密切相关。这些数据有力地表明,WKV诱导的免疫应答赋予针对蚊子阶段的保护,这在很大程度上取决于疟原虫特异性抗体和MCP-1。这一发现为通过接种WKV疫苗阻断疟疾传播提供了新的思路。
As a malaria transmission-blocking vaccine alone does not confer a direct benefit to the recipient, it is necessary to develop a vaccine that not only blocks malaria transmission but also protects vaccinated individuals. In this study we observed that a whole-killed blood-stage vaccine (WKV) not only conferred protection against the blood-stage challenge but also markedly inhibited the transmission of different strains of the malaria parasite. Although the parasitemia is much lower in WKV-immunized mice challenged with malaria parasites, the gametocytemia is comparable between control and immunized mice during the early stages of infection. The depletion of CD4+ T cells prior to the adoptive transfer of parasites into WKV-immunized mice has no effect on the development of the malaria parasite in the mosquito, but the adoptive transfer of the serum from the immunized mice into the parasite-inoculated mice remarkably suppresses the development of malaria parasites in mosquitoes. Furthermore, immunized mice challenged with the malaria parasite generate higher levels of parasite-specific Abs and the inflammatory cytokines MCP-1 and IFN-γ. However, the adoptive transfer of parasite-specific IgG or the depletion of MCP-1, but not IFN-γ, to some extent is closely associated with the suppression of malaria parasite development in mosquitoes. These data strongly suggest that WKV-induced immune responses confer protection against the mosquito stage, which is largely dependent on malaria parasite-specific Abs and MCP-1. This finding sheds new light on blocking malaria transmission through the immunization of individuals with the WKV.
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