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Adjuvant Effect of Bacille Calmette–Guérin on Hepatitis B Vaccine Immunogenicity in the Preterm and Term Newborn

机译:Bacille Calmette–Guérin对新生儿早产和足月乙型肝炎疫苗免疫原性的辅助作用

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摘要

Immunization is key to protecting term and preterm infants from a heightened risk of infection. However, preterm immunity is distinct from that of the term, limiting its ability to effectively respond to vaccines routinely given at birth, such as hepatitis B vaccine (HBV). As part of the Expanded Program on Immunization, HBV is often given together with the live-attenuated vaccine Bacille Calmette–Guérin (BCG), known to activate multiple pattern-recognition receptors. Of note, some clinical studies suggest BCG can enhance efficacy of other vaccines in term newborns. However, little is known about whether BCG can shape Th-polarizing cytokine responses to HBV nor the age-dependency of such effects, including whether they may extend to the preterm. To characterize the effects of BCG on HBV immunogenicity, we studied individual and combined administration of these vaccines to cord newborn and adult human whole blood and mononuclear cells in vitro and to neonatal and adult mice in vivo. Compared to either BCG or HBV alone, (BCG + HBV) synergistically enhanced in vitro whole blood production of IL-1β, while (BCG + HBV) also promoted production of several cytokines/chemokines in all age groups, age-specific enhancement included IL-12p70 in the preterm and GM-CSF in the preterm and term. In human mononuclear cells, (BCG + HBV) enhanced mRNA expression of several genes including CSF2, which contributed to clustering of genes by vaccine treatment via principle component analysis. To assess the impact of BCG on HBV immunization, mice of three different age groups were immunized subcutaneously with, BCG, HBV, (BCG + HBV) into the same site; or BCG and HBV injected into separate sites. Whether injected into a separate site or at the same site, co-administration of BCG with HBV significantly enhanced anti-HBV IgG titers in mice immunized on day of life-0 or -7, respectively, but not in adult mice. In summary, our data demonstrate that innate and adaptive vaccine responses of preterm and term newborns are immunologically distinct. Furthermore, BCG or “BCG-like” adjuvants should be further studied as a promising adjuvantation approach to enhance immunogenicity of vaccines to protect these vulnerable populations.
机译:免疫是保护足月和早产婴儿免受感染风险增加的关键。但是,早产免疫与该术语不同,限制了其对出生时常规接种的疫苗有效反应的能力,例如乙型肝炎疫苗(HBV)。作为扩展免疫计划的一部分,通常将乙肝病毒与减毒活疫苗BacilleCalmette-Guérin(BCG)一起使用,已知该疫苗可激活多种模式识别受体。值得注意的是,一些临床研究表明BCG可以增强足月新生儿中其他疫苗的功效。但是,关于卡介苗是否能够塑造对乙肝病毒的Th极化细胞因子反应,以及此类效应的年龄依赖性(包括它们是否可能延续至早产),人们知之甚少。为了表征BCG对HBV免疫原性的影响,我们研究了将这些疫苗分别和联合给药于体外脐带新生儿和成年人类全血和单核细胞,以及体内给新生儿和成年小鼠的联合治疗。与单独的BCG或HBV相比,(BCG + HBV)协同增强了IL-1β的体外全血产生,而(BCG + HBV)也促进了所有年龄段的几种细胞因子/趋化因子的产生,特定年龄的增强包括IL早产-12p70,早产和足月GM-CSF。在人单核细胞中,(BCG ++ HBV)增强了包括CSF2在内的几个基因的mRNA表达,这通过主成分分析通过疫苗处理促进了基因聚类。为了评估BCG对HBV免疫的影响,将三个不同年龄组的小鼠皮下注射BCG,HBV(BCG + HBV)到同一部位。或将BCG和HBV注射到不同的部位。无论是注射到单独的部位还是在相同的部位,BCG与HBV的共同给药分别显着增强了在生命第0天或-7天免疫的小鼠的抗HBV IgG效价,但在成年小鼠中却没有。总而言之,我们的数据表明早产和足月新生儿的先天性和适应性疫苗反应在免疫学上是不同的。此外,应进一步研究BCG或“ BCG样”佐剂作为一种有前途的佐剂方法,以增强疫苗的免疫原性以保护这些易感人群。

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