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为新生儿期合理选择佐剂可塑造小鼠独特且持久的免疫极化。

Rational adjuvant selection for the neonatal period shapes unique and lasting immune polarization in mice.

作者信息

Chen Chun, Benson Olivia E, Simmons Taylor, Dorsett Chris L, Janczak Katarzyna W, Wiest Matthew J, Farazuddin Mohammad, Baker James R, Wong Pamela T, O'Konek Jessica J

机构信息

Mary H. Weiser Food Allergy Center, Michigan Medicine, Ann Arbor, MI, USA.

Unit for Laboratory Animal Medicine, University of Michigan, Ann Arbor, MI, USA.

出版信息

NPJ Vaccines. 2025 Jul 24;10(1):165. doi: 10.1038/s41541-025-01227-5.

Abstract

A major knowledge gap exists in understanding immune effects of adjuvants in early life. As environmental stimuli shape the infant immune system, adjuvants may also influence this process. Using a neonatal mouse model, we investigated the differential effects of adjuvants in neonates vs. adults. Mice were immunized with an adjuvanted hepatitis B vaccine followed by exposure to ovalbumin to determine whether prior immunization alters subsequent heterologous immune responses. Neonatal immunization with a Th2-biased alum-adjuvanted vaccine predisposed mice to develop Th2-biased immunity to subsequent ovalbumin exposures. Conversely, neonatal immunization with a Th1-polarizing CpG-adjuvanted vaccine resulted in preferential priming of Th1-biased heterologous responses. Immunization in adulthood did not alter heterologous immune responses. Early-life immunization modified the ability of bone marrow DCs to prime Th1/Th2 immune responses, suggesting a role for immune training in these antigen agnostic effects. These data suggest that rational adjuvant selection for early-life vaccines may beneficially shape immune development.

摘要

在理解佐剂对生命早期免疫的影响方面存在重大知识空白。由于环境刺激塑造婴儿免疫系统,佐剂也可能影响这一过程。我们使用新生小鼠模型,研究了佐剂对新生儿和成年人的不同影响。用含佐剂的乙肝疫苗免疫小鼠,随后使其接触卵清蛋白,以确定先前的免疫是否会改变随后的异源免疫反应。用偏向Th2的铝佐剂疫苗对新生小鼠进行免疫,使小鼠倾向于对随后接触的卵清蛋白产生偏向Th2的免疫。相反,用偏向Th1的CpG佐剂疫苗对新生小鼠进行免疫,导致优先启动偏向Th1的异源反应。成年期免疫不会改变异源免疫反应。生命早期免疫改变了骨髓树突状细胞启动Th1/Th2免疫反应的能力,表明免疫训练在这些与抗原无关的效应中发挥作用。这些数据表明,为生命早期疫苗合理选择佐剂可能有益地塑造免疫发育。

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