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

IF 6.5 1区 医学 Q1 IMMUNOLOGY
Chun Chen, Olivia E Benson, Taylor Simmons, Chris L Dorsett, Katarzyna W Janczak, Matthew J Wiest, Mohammad Farazuddin, James R Baker, Pamela T Wong, Jessica J O'Konek
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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.

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新生期合理的佐剂选择塑造了小鼠独特而持久的免疫极化。
在了解佐剂在生命早期的免疫作用方面存在一个主要的知识缺口。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。使用新生小鼠模型,我们研究了佐剂在新生儿和成人中的不同作用。小鼠接种有佐剂的乙型肝炎疫苗,然后暴露于卵清蛋白,以确定事先免疫是否会改变随后的异源免疫反应。用th2偏倚铝佐剂疫苗进行新生儿免疫,可使小鼠对随后的卵清蛋白暴露产生th2偏倚免疫。相反,新生儿接种th1极化cpg佐剂疫苗会导致th1偏倚异源应答的优先启动。成年期免疫接种未改变异源免疫反应。早期免疫改变了骨髓dc启动Th1/Th2免疫应答的能力,提示免疫训练在这些抗原不可知效应中起作用。这些数据表明,早期疫苗的合理佐剂选择可能有利于塑造免疫发育。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
NPJ Vaccines
NPJ Vaccines Immunology and Microbiology-Immunology
CiteScore
11.90
自引率
4.30%
发文量
146
审稿时长
11 weeks
期刊介绍: Online-only and open access, npj Vaccines is dedicated to highlighting the most important scientific advances in vaccine research and development.
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