Centre for International Child Health, Department of Paediatrics, Imperial College London, London, United Kingdom.
Immunobiology Section, UCL Great Ormond Street Institute of Child Health (ICH), London, United Kingdom.
Front Immunol. 2018 Apr 4;9:532. doi: 10.3389/fimmu.2018.00532. eCollection 2018.
Infections take their greatest toll in early life necessitating robust approaches to protect the very young. Here, we review the rationale, current state, and future research directions for one such approach: neonatal immunization. Challenges to neonatal immunization include natural concern about safety as well as a distinct neonatal immune system that is generally polarized against Th1 responses to many stimuli such that some vaccines that are effective in adults are not in newborns. Nevertheless, neonatal immunization could result in high-population penetration as birth is a reliable point of healthcare contact, and offers an opportunity for early protection of the young, including preterm newborns who are deficient in maternal antibodies. Despite distinct immunity and reduced responses to some vaccines, several vaccines have proven safe and effective at birth. While some vaccines such as polysaccharide vaccines have little effectiveness at birth, hepatitis B vaccine can prime at birth and requires multiple doses to achieve protection, whereas the live-attenuated Bacille Calmette-Guérin (BCG), may offer single shot protection, potentially in part heterologous ("non-specific") beneficial effects. Additional vaccines have been studied at birth including those directed against pertussis, pneumococcus, type B and rotavirus providing important lessons. Current areas of research in neonatal vaccinology include characterization of early life immune ontogeny, heterogeneity in and heterologous effects of BCG vaccine formulations, applying systems biology and systems serology, platforms that model age-specific human immunity and discovery and development of novel age-specific adjuvantation systems. These approaches may inform, de-risk, and accelerate development of novel vaccines for use in early life. Key stakeholders, including the general public, should be engaged in assessing the opportunities and challenges inherent to neonatal immunization.
感染在生命早期造成的损失最大，因此需要采取强有力的措施来保护非常年幼的儿童。在这里，我们回顾了一种方法的原理、现状和未来研究方向：新生儿免疫接种。新生儿免疫接种面临的挑战包括对安全性的自然关注，以及新生儿免疫系统的独特性，这种免疫系统通常对许多刺激物产生 Th1 反应的极化，以至于在成年人中有效的一些疫苗在新生儿中无效。然而，新生儿免疫接种可能会导致高人群渗透率，因为出生是可靠的医疗保健接触点，并为年幼的儿童（包括缺乏母体抗体的早产儿）提供早期保护的机会。尽管存在独特的免疫和对某些疫苗的反应减弱，但已经证明几种疫苗在出生时是安全有效的。虽然一些疫苗（如多糖疫苗）在出生时效果不佳，但乙型肝炎疫苗可以在出生时进行免疫接种，并需要多次接种才能达到保护效果，而减毒活卡介苗（BCG）可能提供单次保护，部分原因可能是具有非特异性有益作用。在出生时还研究了其他疫苗，包括针对百日咳、肺炎球菌、B 型和轮状病毒的疫苗，这些研究提供了重要的经验教训。新生儿疫苗学的当前研究领域包括早期生命免疫发生的特征、BCG 疫苗制剂的异质性和非特异性效应、系统生物学和系统血清学的应用、模拟特定年龄人群免疫的平台以及新型年龄特异性佐剂系统的发现和开发。这些方法可以为早期生命中使用的新型疫苗的信息提供、降低风险和加速开发提供信息。包括公众在内的主要利益相关者应该参与评估新生儿免疫接种所固有的机会和挑战。
