Van Braeckel-Budimir Natalija, Harty John T
Department of Microbiology, University of Iowa Iowa, IA, USA.
Front Microbiol. 2014 Jun 6;5:272. doi: 10.3389/fmicb.2014.00272. eCollection 2014.
Malaria is a major global health problem, with severe mortality in children living in sub-Saharan Africa, and there is currently no licensed, effective vaccine. However, vaccine-induced protection from Plasmodium infection, the causative agent of malaria, was established for humans in small clinical trials and for rodents in the 1960s. Soon after, a critical role for memory CD8 T cells in vaccine-induced protection against Plasmodium liver-stage infection was established in rodent models and is assumed to apply to humans. However, these seminal early studies have led to only modest advances over the ensuing years in our understanding the basic features of memory CD8 T cells required for protection against liver-stage Plasmodium infection, an issue which has likely impeded the development of effective vaccines for humans. Given the ethical and practical limitations in gaining mechanistic insight from human vaccine and challenge studies, animal models still have an important role in dissecting the basic parameters underlying memory CD8 T-cell immunity to Plasmodium. Here, we will highlight recent data from our own work in the mouse model of Plasmodium infection that identify quantitative and qualitative features of protective memory CD8 T-cell responses. Finally, these lessons will be discussed in the context of recent findings from clinical trials of vaccine-induced protection in controlled human challenge models.
疟疾是一个重大的全球健康问题，在撒哈拉以南非洲地区生活的儿童中导致严重死亡，目前尚无获得许可的有效疫苗。然而，在20世纪60年代的小型临床试验中为人类建立了疫苗诱导的针对疟原虫感染（疟疾的病原体）的保护作用，并且在啮齿动物中也得到了证实。此后不久，在啮齿动物模型中确定了记忆性CD8 T细胞在疫苗诱导的针对疟原虫肝期感染的保护作用中的关键作用，并假定其也适用于人类。然而，这些开创性的早期研究在随后的几年里，在我们对保护免受肝期疟原虫感染所需的记忆性CD8 T细胞的基本特征的理解方面仅取得了有限的进展，这一问题可能阻碍了人类有效疫苗的开发。鉴于从人类疫苗和激发研究中获取机制性见解存在伦理和实际限制，动物模型在剖析记忆性CD8 T细胞对疟原虫免疫的基本参数方面仍然具有重要作用。在这里，我们将重点介绍我们在疟原虫感染小鼠模型中的最新研究数据，这些数据确定了保护性记忆性CD8 T细胞反应的定量和定性特征。最后，将结合在受控人类激发模型中疫苗诱导保护的临床试验的最新发现来讨论这些经验教训。
