The anti-tetanus immune response of neonatal mice is aulamented by retinoic acid combined with polyriboinosinic:polyribocytidylic acid
The anti-tetanus immune response of neonatal mice is aulamented by retinoic acid combined with polyriboinosinic:polyribocytidylic acid
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DOI：
10.1073/pnas.0506438102
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发表时间：
2005-09-20
影响因子：
11.1
通讯作者：
Ross, AC
中科院分区：
文献类型：
--
作者：
Ma, YF;Ross, AC
新生儿很容易感染传染病，而且通常由于免疫系统不成熟，对常规疫苗的反应很差。在本研究中，我们假设具有生物活性的维甲酸(RA)和干扰素的诱导剂聚核糖核糖核酸(PIC)可以增强新生小鼠的抗破伤风类毒素(TT)疫苗应答。早期使用RA和/或PIC的治疗耐受性良好，并在婴儿期刺激主要的抗TT免疫球蛋白生成，在成年时刺激记忆反应。TT特异性淋巴细胞增殖和1型/2型细胞因子的产生也显著增加。此外，RA和PIC还调节新生儿B细胞、自然杀伤(NK)/NKT细胞和抗原提呈细胞的成熟和/或分化。虽然RA单独增加了新生儿抗TT抗体反应，但它选择性地增加了抗TT IgG1和IL-5，导致了偏斜的2型反应。在成年小鼠中，PIC是一种有效的佐剂，可提高新生儿抗TT免疫球蛋白及其所有免疫球蛋白亚型(IgG1、IgG2a和IgG2b)，并诱导重要的1型细胞因子TT特异性干扰素-γ；然而，单独使用PIC并不能改善记忆反应。RA和PIC联合用药在提高一次和二次抗TT免疫球蛋白应答和免疫球蛋白G亚型方面比单独使用任何一种药物更有效。此外，RA加PIC可增加TT特异性的干扰素-γ和IL-5，这表明该组合有效地促进了新生小鼠的1型和2型反应。因此，RA联合PIC是一种营养免疫干预措施，似乎有希望成为早期疫苗接种的佐剂。
Neonates are highly susceptible to infectious diseases and, in general, respond poorly to conventional vaccines due to immaturity of the immune system. In the present study, we hypothesized that the anti-tetanus toxoid (TT) vaccine response of neonatal mice could be enhanced by retinoic acid (RA), a bioactive retinoid, and polyriboinosinic:polyribocytidylic acid (PIC), an inducer of IFN. Early-life treatments with RA and/or PIC were well tolerated and stimulated both primary anti-TT IgG production in infancy and the memory response in adulthood. TT-specific lymphocyte proliferation and type 1/type 2 cytokine production were also significantly augmented. In addition, RA and PIC modulated the maturation and/or differentiation of neonatal B cells, natural killer (NK)/NKT cells, and antigen-presenting cells. Although RA alone increased the neonatal anti-TT antibody response, it selectively increased anti-TT IgG1 and IL-5, resulting in a skewed type 2 response. PIC, a potent adjuvant in adult mice, elevated neonatal anti-TT IgG as well as all IgG isotypes (IgG1, IgG2a, and IgG2b) and induced TT-specific IFN-gamma, an important type 1 cytokine; however, PIC alone failed to benefit the memory response. The combination of RA plus PIC was more potent than either agent alone in elevating primary and secondary anti-TT IgG responses as well as IgG isotypes. Moreover, RA plus PIC increased TT-specific IFN-gamma and IL-5, suggesting the combination effectively promoted both type 1 and type 2 responses in neonatal mice. Thus, RA combined with PIC, a nutritional-immunological intervention, seems promising as an adjuvant for early-life vaccination.