Humoral protection against mosquito bite-transmitted Plasmodium falciparum infection in humanized mice.
Humoral protection against mosquito bite-transmitted Plasmodium falciparum infection in humanized mice.
复制标题
人源化小鼠中针对蚊虫叮咬传播的恶性疟原虫感染的体液保护。
DOI：
10.1038/s41541-017-0028-2
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发表时间：
2017
期刊：
影响因子：
9.2
通讯作者：
Chakravarty,Suma
中科院分区：
文献类型：
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作者：
Sack,BrandonK;Mikolajczak,SebastianA;Fishbaugher,Matthew;Vaughan,AshleyM;Flannery,ErikaL;Nguyen,Thao;Betz,Will;JaneNavarro,Mary;Foquet,Lander;Steel,RyanWJ;Billman,ZacharyP;Murphy,SeanC;Hoffman,StephenL;Chakravarty,Suma
预防感染的疟疾疫苗将成为持续消除疟疾的重要新工具，针对主要人类疟疾寄生虫恶性疟原虫（Pf）的此类疫苗正在紧锣密鼓地开发中。疫苗产生的抗体可以阻止寄生虫感染的初始阶段，此时子孢子通过蚊子叮咬沉积到皮肤中，然后以肝脏为目标进行进一步发育。然而，目前还没有标准化的体内临床前模型可以测量抗体特异性针对蚊虫叮咬感染子孢子的抑制活性。在这里，我们使用人肝嵌合小鼠作为挑战模型来评估抗体对天然子孢子感染的预防作用。我们证明这些小鼠始终通过蚊虫叮咬感染 Pf，并且可以将这种挑战与来自免疫血清的单克隆抗体或多克隆人 IgG 的被动转移相结合，以使用生物发光成像测量抗体介导的寄生虫感染阻断。该方法可用于向下选择功能性抗体并研究临床试验中保护的机制或免疫相关性，从而为合理的疫苗优化提供信息。
A malaria vaccine that prevents infection will be an important new tool in continued efforts of malaria elimination, and such vaccines are under intense development for the major human malaria parasitePlasmodium falciparum(Pf). Antibodies elicited by vaccines can block the initial phases of parasite infection when sporozoites are deposited into the skin by mosquito bite and then target the liver for further development. However, there are currently no standardized in vivo preclinical models that can measure the inhibitory activity of antibody specificities againstPfsporozoite infection via mosquito bite. Here, we use human liver-chimeric mice as a challenge model to assess prevention of naturalPfsporozoite infection by antibodies. We demonstrate that these mice are consistently infected withPfby mosquito bite and that this challenge can be combined with passive transfer of either monoclonal antibodies or polyclonal human IgG from immune serum to measure antibody-mediated blocking of parasite infection using bioluminescent imaging. This methodology is useful to down-select functional antibodies and to investigate mechanisms or immune correlates of protection in clinical trials, thereby informing rational vaccine optimization.