Flanagan Katie L, Mwangi Tabitha, Plebanski Magdalena, Odhiambo Kennedy, Ross Amanda, Sheu Eric, Kortok Moses, Lowe Brett, Marsh Kevin, Hill Adrian V S
Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford, United Kingdom.
Am J Trop Med Hyg. 2003 Apr;68(4):421-30.
Thrombospondin-related adhesive protein (TRAP) of Plasmodium falciparum is currently being tested in human vaccine studies. However, its natural reactivity in the field remains poorly characterized. More than 40% of 217 Kenyan donors responded in an ex vivo interferon-gamma (IFN-gamma) enzyme-linked immunospot (ELISPOT) assay to at least one of 14 20mer peptides spanning 42% of the antigen. Reactivity was comparable from early childhood (>1 year of age) to old age, and the maximal precursor frequency of TRAP-specific cells to all 14 peptides was 1 in 4,000. Prospective follow-up for one year indicated that these low-level ex vivo responses to TRAP did not protect against the subsequent development of malaria. Retesting of selected donors after one year showed a complete change in the reactivity pattern, suggesting that malaria-specific ex vivo IFN-gamma ELISPOT assay responses are short lived in naturally exposed donors, even to conserved epitopes. This study provides important information regarding natural reactivity to a key malaria antigen.
恶性疟原虫的血小板反应蛋白相关黏附蛋白（TRAP）目前正在人体疫苗研究中进行测试。然而，其在自然环境中的反应性仍未得到充分表征。在一项体外干扰素-γ（IFN-γ）酶联免疫斑点（ELISPOT）试验中，217名肯尼亚献血者中有超过40%的人对覆盖该抗原42%的14种20肽中的至少一种有反应。从幼儿期（>1岁）到老年，反应性相当，TRAP特异性细胞对所有14种肽的最大前体频率为4000分之一。为期一年的前瞻性随访表明，这些对TRAP的低水平体外反应并不能预防随后疟疾的发生。一年后对选定献血者的重新检测显示反应模式完全改变，这表明即使是对保守表位，自然暴露的献血者中疟疾特异性体外IFN-γ ELISPOT试验反应也是短暂的。这项研究提供了关于对一种关键疟疾抗原的自然反应性的重要信息。
