Coelho-Dos-Reis Jordana Grazziela, Li Xiangming, Tsuji Moriya
Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, Minas Gerais, Brazil.
Aaron Diamond AIDS Research Center, Affiliate of The Rockefeller University, New York, NY, USA.
F1000Res. 2018 May 30;7. doi: 10.12688/f1000research.13794.1. eCollection 2018.
The inability to elicit strong and durable cellular responses is a major obstacle in the development of successful vaccines, in particular those against malaria. In this regard, the generation of novel adjuvants that will potently boost cell-mediated immunity induced by candidate vaccines is helpful. We and others have found a glycolipid, called α-galactosylceramide (α-GalCer), which could be presented on CD1d expressed by antigen-presenting cells (APCs) and stimulate natural killer T (NKT) cells. This triggers the activation/maturation of APCs, particularly dendritic cells (DCs). By activating NKT cells and subsequently DCs, α-GalCer has been shown to enhance adaptive immune responses, particularly of CD8 T cells, induced by the vaccines. More recently, we identified an analogue of α-GalCer, which can display a potent adjuvant activity in conjunction with malaria vaccines in mice and non-human primates. It is anticipated that CD1d-binding, NKT cell-stimulating glycolipids will be tested as adjuvants in humans in the near future.
无法引发强烈且持久的细胞反应是成功开发疫苗（尤其是抗疟疾疫苗）的主要障碍。在这方面，研发能够有效增强候选疫苗诱导的细胞介导免疫的新型佐剂会有所帮助。我们及其他研究人员发现了一种名为α-半乳糖神经酰胺（α-GalCer）的糖脂，它可呈递于抗原呈递细胞（APC）所表达的CD1d上，并刺激自然杀伤T（NKT）细胞。这会触发APC的激活/成熟，尤其是树突状细胞（DC）。通过激活NKT细胞并随后激活DC，α-GalCer已被证明可增强疫苗诱导的适应性免疫反应，尤其是CD8 + T细胞的反应。最近，我们鉴定出了α-GalCer的一种类似物，它在小鼠和非人类灵长类动物中与疟疾疫苗联合使用时可表现出强大的佐剂活性。预计与CD1d结合、刺激NKT细胞的糖脂在不久的将来将作为佐剂在人体中进行测试。
