Neonatal and infant immunity differs from that of adults in both the innate and adaptive arms, which are critical contributors to immune-mediated clearance of infection and memory responses elicited during vaccination. The tuberculosis (TB) research community has openly admitted to a vacuum of knowledge about neonatal and infant immune responses to Mycobacterium tuberculosis (Mtb) infection, especially in the functional and phenotypic attributes of memory T cell responses elicited by the only available vaccine for TB, the Bacillus Calmette-Guérin (BCG) vaccine. Although BCG vaccination has variable efficacy in preventing pulmonary TB during adolescence and adulthood, 80% of endemic TB countries still administer BCG at birth because it has a good safety profile and protects children from severe forms of TB. As such, new vaccines must work in conjunction with BCG at birth and, thus, it is essential to understand how BCG shapes the immune system during the first months of life. However, many aspects of the neonatal and infant immune response elicited by vaccination with BCG remain unknown, as only a handful of studies have followed BCG responses in infants. Furthermore, most animal models currently used to study TB vaccine candidates rely on adult-aged animals. This presents unique challenges when transitioning to human trials in neonates or infants. In this Review, we focus on vaccine development in the field of TB and compare the relative utility of animal models used thus far to study neonatal and infant immunity. We encourage the development of neonatal animal models for TB, especially the use of pigs.

中文翻译：

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结核疫苗开发的新生儿和婴儿免疫力：年龄匹配动物模型的重要性。


新生儿和婴儿的先天免疫和适应性免疫与成人的免疫不同，它们是免疫介导的感染清除和疫苗接种过程中引发的记忆反应的关键因素。结核病 (TB) 研究界公开承认，对于新生儿和婴儿对结核分枝杆菌(Mtb) 感染的免疫反应缺乏了解，特别是在唯一可用的结核病疫苗引发的记忆 T 细胞反应的功能和表型属性方面，卡介苗 (BCG) 疫苗。尽管卡介苗接种在预防青春期和成年期肺结核方面的功效各不相同，但 80% 的结核病流行国家仍然在出生时接种卡介苗，因为它具有良好的安全性并可保护儿童免受严重结核病的侵害。因此，新疫苗必须在出生时与卡介苗结合使用，因此了解卡介苗在生命最初几个月如何塑造免疫系统至关重要。然而，卡介苗疫苗接种引起的新生儿和婴儿免疫反应的许多方面仍然未知，因为只有少数研究跟踪了婴儿的卡介苗反应。此外，目前用于研究结核病候选疫苗的大多数动物模型都依赖于成年动物。当过渡到新生儿或婴儿的人体试验时，这提出了独特的挑战。在这篇综述中，我们重点关注结核病领域的疫苗开发，并比较迄今为止用于研究新生儿和婴儿免疫的动物模型的相对效用。我们鼓励开发结核病新生儿动物模型，特别是使用猪。