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
Mary H. Weiser Food Allergy Center, Michigan Medicine, Ann Arbor, MI, USA.
Unit for Laboratory Animal Medicine, University of Michigan, Ann Arbor, MI, USA.
NPJ Vaccines. 2025 Jul 24;10(1):165. doi: 10.1038/s41541-025-01227-5.
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.
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。