Ndure Jorjoh, Flanagan Katie L
Infant Immunology Group, Vaccinology Theme, Medical Research Council Laboratories Fajara, The Gambia.
Vaccine and Infectious Diseases Laboratory, Department of Immunology, Monash University Melbourne, VIC, Australia.
Front Microbiol. 2014 Sep 11;5:477. doi: 10.3389/fmicb.2014.00477. eCollection 2014.
Human newborns and infants are bombarded with multiple pathogens on leaving the sterile intra-uterine environment, and yet have suboptimal innate immunity and limited immunological memory, thus leading to increased susceptibility to infections in early life. They are thus the target age group for a host of vaccines against common bacterial and viral pathogens. They are also the target group for many vaccines in development, including those against tuberculosis (TB), malaria, and HIV infection. However, neonatal and infant responses too many vaccines are suboptimal, and in the case of the polysaccharide vaccines, it has been necessary to develop the alternative conjugated formulations in order to induce immunity in early life. Immunoregulatory factors are an intrinsic component of natural immunity necessary to dampen or control immune responses, with the caveat that they may also decrease immunity to infections or lead to chronic infection. This review explores the key immunoregulatory factors at play in early life, with a particular emphasis on regulatory T cells (Tregs). It goes on to explore the role that Tregs play in limiting vaccine immunogenicity, and describes animal and human studies in which Tregs have been depleted in order to enhance vaccine responses. A deeper understanding of the role that Tregs play in limiting or controlling vaccine-induced immunity would provide strategies to improve vaccine immunogenicity in this critical age group. New adjuvants and drugs are being developed that can transiently suppress Treg function, and their use as part of human vaccination strategies against infections is becoming a real prospect for the future.
人类新生儿和婴儿在离开无菌的子宫内环境后会受到多种病原体的侵袭，但他们的先天免疫功能欠佳，免疫记忆有限，因此在生命早期更容易受到感染。所以，他们是许多针对常见细菌和病毒病原体疫苗的目标年龄组。他们也是许多正在研发的疫苗的目标群体，包括那些针对结核病、疟疾和艾滋病毒感染的疫苗。然而，新生儿和婴儿对许多疫苗的反应并不理想，就多糖疫苗而言，有必要开发替代的结合疫苗配方，以便在生命早期诱导免疫。免疫调节因子是天然免疫的一个内在组成部分，对于抑制或控制免疫反应是必需的，但需要注意的是，它们也可能降低对感染的免疫力或导致慢性感染。本综述探讨了生命早期起作用的关键免疫调节因子，特别强调了调节性T细胞（Tregs）。接着探讨了Tregs在限制疫苗免疫原性方面所起的作用，并描述了为增强疫苗反应而使Tregs耗竭的动物和人体研究。更深入地了解Tregs在限制或控制疫苗诱导免疫方面所起的作用，将为提高这一关键年龄组的疫苗免疫原性提供策略。正在开发能够短暂抑制Treg功能的新型佐剂和药物，将其作为人类抗感染疫苗接种策略的一部分，在未来正成为一种切实可行的前景。
