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Induction of Mosquitocidal Activity in Mice Immunized with Anopheles gambiae Midgut cDNA

机译：冈比亚按蚊中肠cDNA免疫的小鼠的杀鼠活性的诱导

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Vaccines that induce mosquito-killing (mosquitocidal) activity could substantially reduce the transmission of certain mosquito-borne diseases, especially vaccines against African malaria vectors, such as the mosquito Anopheles gambiae. To generate and characterize antimosquito immunity we immunized groups of mice with two individual A. gambiae midgut cDNAs, Ag-Aper1 (a secreted peritrophic matrix protein) and AgMuc1 (a midgut-bound mucin), and an A. gambiae midgut cDNA library from blood-fed mosquitoes. We observed significantly increased mortality among mosquitoes that fed on either the AgMuc1- or the cDNA library-immunized mice compared to that of controls, but no differences were observed among those fed on Ag-Aper1-immunized mice. Analysis of the humoral and cellular immune responses from mice showed that the induced mosquitocidal effect was associated with immune profiles characterized by elevated tumor necrosis factor alpha and gamma interferon cytokine levels and very low antibody titers. Furthermore, an additional immunization of cDNA library-immunized mice with midgut protein shifted immunity toward a Th2-type immune response, characterized by elevated antibody titers and high interleukin-5 and interleukin-10 cytokine levels; importantly, mosquitoes feeding on these mice exhibited no undo mortality. Finally, when immune sera was ingested by mosquitoes through a membrane feeder, no effect on mosquito mortality was observed, indicating that serum factors alone were not responsible for the mosquitocidal effect. Our results demonstrate that mosquitocidal immunity in mice can be consistently generated by midgut cDNA immunization and suggest this cDNA-induced mosquitocidal immunity is cell mediated.
机译：诱导灭蚊活性的疫苗可以大大减少某些蚊媒疾病的传播，特别是针对非洲疟疾媒介的疫苗，例如冈比亚按蚊（em按蚊）。为了产生和表征抗蚊免疫力，我们用两个单独的 A免疫小鼠组。冈比亚中肠cDNA， Ag-Aper1 （一种分泌的营养丰富的基质蛋白）和 AgMuc1 （一种与中肠结合的粘蛋白）和一个 A。食血蚊子的冈比亚中肠cDNA文库我们观察到饲喂 AgMuc1 -或cDNA文库免疫小鼠的蚊子与对照组相比，死亡率显着增加，但是饲喂 Ag-Aper1 <免疫的小鼠。对小鼠的体液和细胞免疫应答的分析表明，诱导的灭蚊作用与以肿瘤坏死因子α和γ干扰素细胞因子水平升高和抗体滴度非常低为特征的免疫特征有关。此外，用中肠蛋白对cDNA文库免疫的小鼠进行的另一次免疫将免疫转向Th2型免疫反应，其特征是抗体效价升高以及白介素5和白介素10细胞因子水平升高;重要的是，以这些小鼠为食的蚊子没有表现出致死性。最后，当蚊子通过膜喂食器摄取免疫血清时，未观察到对蚊子死亡率的影响，这表明仅血清因子与灭蚊作用无关。我们的结果表明，中肠cDNA免疫可始终如一地产生小鼠的灭蚊免疫力，并表明这种cDNA诱导的灭蚊免疫是细胞介导的。

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