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Abstract：
Infections are most common and most severe at the extremes of age, the young and the elderly. Vaccination can be a key approach to enhance immunogenicity and protection against pathogens in these vulnerable populations, who have a functionally distinct immune system compared to other age groups. More than 50% of the vaccine market is for pediatric use, yet to date vaccine development is often empiric and not tailored to molecular distinctions in innate and adaptive immune activation in early life. With modern vaccine development shifting from whole-cell based vaccines to subunit vaccines also comes the need for formulations that can elicit a CD8+ T cell response when needed, for example, by promoting antigen cross-presentation. While our group and others have identified many cellular and molecular determinants of successful activation of antigen-presenting cells, B cells and CD4+ T cells in early life, much less is known about the ontogeny of CD8+ T cell induction. In this review, we summarize the literature pertaining to the frequency and phenotype of newborn and infant CD8+ T cells, and any evidence of induction of CD8+ T cells by currently licensed pediatric vaccine formulations. In addition, we review the molecular determinants of antigen cross-presentation on MHC I and successful CD8+ T cell induction and discuss potential distinctions that can be made in children. Finally, we discuss recent advances in development of novel adjuvants and provide future directions for basic and translational research in this area.
摘要：
感染在极端年龄是最常见和最严重的，年轻人和老年人。疫苗接种可能是增强这些脆弱人群的免疫原性和对病原体的保护的关键方法。与其他年龄组相比，他们的免疫系统功能不同。超过50%的疫苗市场是用于儿科的，迄今为止，疫苗开发通常是经验性的，而不是针对早期先天和适应性免疫激活的分子差异。随着现代疫苗开发从基于全细胞的疫苗转向亚单位疫苗，也需要在需要时引起CD8+T细胞反应的制剂。例如,通过促进抗原交叉呈递。虽然我们的团队和其他人已经确定了许多成功激活抗原呈递细胞的细胞和分子决定因素，早期的B细胞和CD4+T细胞，人们对CD8+T细胞诱导的个体发育知之甚少。在这次审查中,我们总结了有关新生儿和婴儿CD8+T细胞的频率和表型的文献，以及目前许可的儿科疫苗制剂诱导CD8+T细胞的任何证据。此外,我们回顾了MHCI抗原交叉呈递和成功诱导CD8+T细胞的分子决定因素，并讨论了儿童中可能产生的区别。最后,我们讨论了新型佐剂开发的最新进展，并为该领域的基础和转化研究提供了未来的方向。
