Protective cellular immunity against influenza virus induced by plasmid inoculation of newborn mice.
Protective cellular immunity against influenza virus induced by plasmid inoculation of newborn mice.
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DOI：
10.1155/1998/50472
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发表时间：
1998-01-01
期刊：
影响因子：
--
通讯作者：
Bona, C
中科院分区：
文献类型：
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作者：
Bot, A;Bot, S;Bona, C
新生生物体表现出对感染因子或常规疫苗产生有效免疫应答的内在缺陷。尽管低剂量的抗原触发次优反应，但较高剂量通常与耐受诱导相关。我们研究了表达流感病毒核蛋白的质粒在新生小鼠中引发特异性细胞免疫应答的能力。我们发现，持续暴露于抗原质粒接种的新生儿导致一个积极的启动特定的CTL，而不是耐受诱导。CTL对多种A型流感病毒株具有交叉反应性，并产生IFN γ，但不产生IL-4。新生儿质粒接种引发的免疫在肺病毒清除以及流感病毒致死性攻击后的存活率方面具有保护性。而质粒在注射部位的持久性在接种后3个月的成年小鼠中很容易证明，新生小鼠免疫接种后3个月没有显示质粒，注射后1个月非常少。因此，基于DNA的新生儿免疫接种可能被证明是一种有效和安全的疫苗接种策略，用于诱导针对在生命早期引起严重传染病的微生物的细胞免疫。
Neonate organisms display an intrinsic disability to mount effective immune responses to infectious agents or conventional vaccines. Whereas low doses of antigens trigger a suboptimal response, higher doses are frequently associated with tolerance induction. We investigated the ability of a plasmid-expressing nucleoprotein of influenza virus to prime a specific cellular immune response when administered to newborn mice. We found that persistent exposure to antigen following plasmid inoculation of neonates leads to a vigorous priming of specific CTLs rather than tolerance induction. The CTLs were cross-reactive against multiple strains of type A influenza viruses and produced IFNgamma but no IL-4. The immunity triggered by plasmid inoculation of neonates was protective in terms of pulmonary virus clearance as well as survival rate following lethal challenge with influenza virus. Whereas the persistence of the plasmid at the site of injection was readily demonstrable in adult mice at 3 months after inoculation, mice immunized as newborns displayed no plasmid at 3 months and very little at 1 month after injection. Thus, DNA-based immunization of neonates may prove an effective and safe vaccination strategy for induction of cellular immunity against microbes that cause serious infectious diseases in the early period of life.