首页> 外文期刊>Infection and immunity >Heterologous Priming-Boosting with DNA and Modified Vaccinia Virus Ankara Expressing Tryparedoxin Peroxidase Promotes Long-Term Memory against Leishmania major in Susceptible BALB/c Mice
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Heterologous Priming-Boosting with DNA and Modified Vaccinia Virus Ankara Expressing Tryparedoxin Peroxidase Promotes Long-Term Memory against Leishmania major in Susceptible BALB/c Mice

机译:DNA和修饰的痘苗病毒安卡拉表达Tryparedoxin过氧化物酶的异源启动-增强促进了对易感BALB / c小鼠主要利什曼原虫的长期记忆

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Leishmaniasis affects 12 million people, but there are no vaccines in routine clinical use. Th1 polarizing vaccines that elicit long-term protection are required to prevent disease in susceptible populations. We recently showed that heterologous priming-boosting with tryparedoxin peroxidase (TRYP) DNA followed by TRYP-modified vaccinia virus Ankara (TRYP MVA) protected susceptible BALB/c mice from Leishmania major. Here we compared treatment with TRYP DNA with treatment with TRYP DNA/TRYP MVA. We found that equivalent levels of protection during the postvaccination effector phase correlated with equivalent levels of serum immunoglobulin G2a and gamma interferon (IFN-γ) in draining lymph nodes. In contrast, challenge infection during the memory phase revealed that there was enhanced clinical efficacy with TRYP DNA/TRYP MVA. This correlated with higher levels of effector phase splenic IFN-γ, sustained prechallenge levels of memory phase IFN-γ, and a more polarized post-L. major challenge Th1 response compared to the Th2/Treg response. Thus, TRYP DNA/TRYP MVA, but not TRYP DNA alone, provides long-term protection against murine leishmaniasis.
机译:利什曼病影响1200万人,但常规临床中没有疫苗。需要Th1极化疫苗引起长期保护,以预防易感人群中的疾病。我们最近发现,先用tryparedoxin过氧化物酶(TRYP)DNA进行异源启动,然后用TRYP修饰的牛痘病毒安卡拉(TRYP MVA)保护易感的BALB / c小鼠免于 Leishmania 。在这里,我们将TRYP DNA处理与TRYP DNA / TRYP MVA处理进行了比较。我们发现,在免疫接种后效应子阶段的等效保护水平与引流淋巴结中的血清免疫球蛋白G2a和γ干扰素(IFN-γ)的等效水平相关。相反,在记忆阶段的挑战性感染显示TRYP DNA / TRYP MVA的临床疗效增强。这与较高水平的效应相脾脏IFN-γ,持续的挑战前水平的记忆相IFN-γ和极化后的L有关。与Th2 / T reg 反应相比,主要的挑战Th1反应。因此,TRYP DNA / TRYP MVA不能单独提供TRYP DNA / TRYP MVA的长期保护,以抵抗鼠类利什曼病。

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