HIV-1 vaccine-specific responses induced by Listeria vector vaccines are maintained in mice subsequently infected with a model helminth parasite, Schistosoma mansoni.

HIV-1 vaccine-specific responses induced by Listeria vector vaccines are maintained in mice subsequently infected with a model helminth parasite, Schistosoma mansoni.
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在随后感染模型蠕虫寄生虫曼氏血吸虫的小鼠中,李斯特菌载体疫苗诱导的 HIV-1 疫苗特异性反应得以维持。

DOI:
10.1016/j.vaccine.2013.09.067
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发表时间:
2013
期刊:
影响因子:
5.5
通讯作者:
Harn,DonaldA
Harn,DonaldA
中科院分区:
医学3区
文献类型:
--
作者:
Shollenberger,LisaM;Bui,CacT;Paterson,Yvonne;Nyhoff,Lindsay;Harn,DonaldA

文献摘要

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在蠕虫寄生虫和艾滋病毒/艾滋病共同流行的地区,婴儿通常在感染免疫调节蠕虫寄生虫之前接种疫苗。蠕虫感染引起的系统性Th 2偏向和免疫抑制会减少细胞介导的对破伤风类毒素和卡介苗等疫苗的反应。因此,我们询问接种后蠕虫感染是否改变了已经建立的疫苗诱导的免疫应答。在我们的模型中,使用李斯特菌疫苗载体(Lm-Gag)以初免-加强的方式对小鼠接种HIV-1 Gag,然后感染人类蠕虫寄生虫曼氏血吸虫。这使我们能够确定蠕虫感染后是否维持或改变了已建立的疫苗应答。我们的第二个目标是询问接种后蠕虫感染是否改变了接受者对第二次加强免疫的反应能力。在这里,我们比较了未感染的小鼠,受感染的小鼠和感染的小鼠之间的反应,这些小鼠被给予驱虫剂,这与加强免疫或四周前同时发生,以及与未加强免疫的小鼠进行比较。我们报道了李斯特菌HIV-1疫苗产生的HIV-1疫苗特异性应答在随后的慢性寄生虫感染后仍能维持,这进一步证明李斯特菌疫苗诱导了有效的疫苗特异性应答,可以抵抗蠕虫感染。我们还能够证明,给予第二种李斯特菌明显增强免疫反应,受寄生虫感染或驱虫治疗的影响最小。令人惊讶的是,我们也观察到增强的抗体反应,艾滋病毒Gag接种小鼠随后感染的染色体。
In areas co-endemic for helminth parasites and HIV/AIDS, infants are often administered vaccines prior to infection with immune modulatory helminth parasites. Systemic Th2 biasing and immune suppression caused by helminth infection reduces cell-mediated responses to vaccines such as tetanus toxoid and BCG. Therefore, we asked if infection with helminthes post-vaccination, alters already established vaccine induced immune responses. In our model, mice are vaccinated against HIV-1 Gag using aListeriavaccine vector (Lm-Gag) in a prime-boost manner, then infected with the human helminth parasiteSchistosoma mansoni. This allows us to determine if established vaccine responses are maintained or altered after helminth infection. Our second objective asked if helminth infection post-vaccination alters the recipient's ability to respond to a second boost. Here we compared responses between uninfected mice, schistosome infected mice, and infected mice that were given an anthelminthic, which occurred coincident with the boost or four weeks prior, as well as comparing to un-boosted mice. We report that HIV-1 vaccine-specific responses generated byListeriavector HIV-1 vaccines are maintained following subsequent chronic schistosome infection, providing further evidence thatListeriavector vaccines induce potent vaccine-specific responses that can withstand helminth infection. We also were able to demonstrate that administration of a secondListeriaboost, which markedly enhanced the immune response, was minimally impacted by schistosome infection, or anthelminthic therapy. Surprisingly, we also observed enhanced antibody responses to HIV Gag in vaccinated mice subsequently infected with schistosomes.