Immune response of neonates elicited by somatic transgene vaccination with naked DNA.
Immune response of neonates elicited by somatic transgene vaccination with naked DNA.
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DOI：
10.2741/a181
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发表时间：
1997-05
期刊：
影响因子：
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通讯作者：
A. Bot;S. Antohi;C. Bona
中科院分区：
文献类型：
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作者：
A. Bot;S. Antohi;C. Bona
新生儿表现出较低的免疫反应性和较高的高剂量耐受性。新生儿和成人淋巴细胞或抗原提呈细胞(APC)在数量和功能上的差异，解释了出生后发育早期的特殊免疫反应。新生儿淋巴细胞和APC数量的减少以及T细胞反应性的改变是造成新生儿耐受阈值低的主要因素。考虑到这些特殊性，设计有效的新生儿疫苗带来了极大的困难。我们假设，持续暴露于低剂量的抗原可以避免高区耐受，反而可能导致效应器和记忆细胞的有效扩张。事实上，给新生小鼠接种编码流感病毒核蛋白(NP)或血凝素(HA)的质粒会导致特异性细胞毒(CTL)、辅助性(Th)和B细胞的启动，而不是诱导无反应性。新生时用裸露DNA免疫的小鼠，后来用致命剂量的流感病毒攻击，显示出显著的保护作用。因此，DNA免疫可能是预防婴幼儿严重传染病的一种很有前途的策略。
Neonates display lower immune responsiveness and higher susceptibility for high-dose tolerance. Quantitative as well as functional differences between the neonatal and adult lymphocytes or antigen presenting cells (APC) respectively, explain the particular immune responsiveness during the early stages of the postnatal development. Reduced numbers of lymphocytes and APCs as well as a modified responsiveness of T cells in neonates, are the main factors that account for the low threshold of tolerance in newborns. Taking into account these particularities, the design of effective vaccines for neonates poses significant difficulties. We hypothesized that a continuous exposure to low doses of antigens may avoid high-zone tolerance and may lead instead, to effective expansion of effector and memory cells. Indeed, inoculation of newborn mice with plasmids encoding nucleoprotein (NP) or hemagglutinin (HA) of influenza virus, led to the priming of specific cytotoxic (CTL), helper (Th) and B cells, rather than induction of unresponsiveness. Mice immunized as neonates with naked DNA and challenged later with lethal doses of influenza virus, displayed significant protection. Thus, DNA immunization may be a promising strategy for vaccination against serious infectious diseases of infants and children.