Aidoo M, Lalvani A, Allsopp C E, Plebanski M, Meisner S J, Krausa P, Browning M, Morris-Jones S, Gotch F, Fidock D A
Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital.
Lancet. 1995 Apr 22;345(8956):1003-7. doi: 10.1016/s0140-6736(95)90754-8.
Several cellular and humoral mechanisms probably play a role in natural immunity to Plasmodium falciparum malaria, but the development of an effective vaccine has been impeded by uncertainty as to which antigens are targeted by protective immune responses. Experimental models of malaria have shown that cytotoxic T lymphocytes (CTL) which kill parasite-infected hepatocytes can provide complete protective immunity against certain species of Plasmodium in mice, and studies in The Gambia have provided indirect evidence that CTL play a protective role against P falciparum in humans. By using an HLA-based approach, termed reverse immunogenetics, we have previously identified peptide epitopes for CTL in liver-stage antigen-1 and the circumsporozoite protein of P falciparum. We have extended this work to identify CTL epitopes for HLA class I antigens that are found in most individuals from Caucasian and African populations. Most of these epitopes are in conserved regions of P falciparum. CTL peptide epitopes were found in a further two antigens, thrombospondin-related anonymous protein and sporozoite threonine and asparagine rich protein, indicating that a subunit vaccine designed to induce a protective CTL response may need to include parts of several parasite antigens. However, CTL levels in both children with malaria and in semi-immune adults from an endemic area were low suggesting that boosting these low levels by immunisation might provide substantial or even complete protection against infection and disease.
几种细胞和体液机制可能在对恶性疟原虫疟疾的天然免疫中发挥作用，但由于保护性免疫反应所针对的抗原尚不明确，有效的疫苗开发受到了阻碍。疟疾的实验模型表明，杀死被寄生虫感染的肝细胞的细胞毒性T淋巴细胞（CTL）能够为小鼠提供针对某些疟原虫物种的完全保护性免疫，并且在冈比亚的研究提供了间接证据，表明CTL在人类中对恶性疟原虫发挥保护作用。通过使用一种基于HLA的方法，即反向免疫遗传学，我们先前已在恶性疟原虫的肝期抗原-1和环子孢子蛋白中鉴定出CTL的肽表位。我们将这项工作扩展到鉴定在白种人和非洲人群的大多数个体中发现的HLA I类抗原的CTL表位。这些表位中的大多数位于恶性疟原虫的保守区域。在另外两种抗原，即血小板反应蛋白相关无名蛋白和富含苏氨酸和天冬酰胺的子孢子蛋白中也发现了CTL肽表位，这表明设计用于诱导保护性CTL反应的亚单位疫苗可能需要包含几种寄生虫抗原的部分。然而，疟疾患儿和来自流行地区的半免疫成年人中的CTL水平都很低，这表明通过免疫来提高这些低水平可能会提供对感染和疾病的实质性甚至完全保护。
