Saeed Maha, Roeffen Will, Alexander Neal, Drakeley Christopher J, Targett Geoffrey A T, Sutherland Colin J
Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom.
PLoS One. 2008 May 28;3(5):e2280. doi: 10.1371/journal.pone.0002280.
The asexual blood stages of the human malaria parasite Plasmodium falciparum produce highly immunogenic polymorphic antigens that are expressed on the surface of the host cell. In contrast, few studies have examined the surface of the gametocyte-infected erythrocyte.
METHODOLOGY/PRINCIPAL FINDINGS: We used flow cytometry to detect antibodies recognising the surface of live cultured erythrocytes infected with gametocytes of P. falciparum strain 3D7 in the plasma of 200 Gambian children. The majority of children had been identified as carrying gametocytes after treatment for malaria, and each donated blood for mosquito-feeding experiments. None of the plasma recognised the surface of erythrocytes infected with developmental stages of gametocytes (I-IV), but 66 of 194 (34.0%) plasma contained IgG that recognised the surface of erythrocytes infected with mature (stage V) gametocytes. Thirty-four (17.0%) of 200 plasma tested recognised erythrocytes infected with trophozoites and schizonts, but there was no association with recognition of the surface of gametocyte-infected erythrocytes (odds ratio 1.08, 95% C.I. 0.434-2.57; P = 0.851). Plasma antibodies with the ability to recognise gametocyte surface antigens (GSA) were associated with the presence of antibodies that recognise the gamete antigen Pfs 230, but not Pfs48/45. Antibodies recognising GSA were associated with donors having lower gametocyte densities 4 weeks after antimalarial treatment.
CONCLUSIONS/SIGNIFICANCE: We provide evidence that GSA are distinct from antigens detected on the surface of asexual 3D7 parasites. Our findings suggest a novel strategy for the development of transmission-blocking vaccines.
人类疟原虫恶性疟原虫的无性血液阶段产生高度免疫原性的多态性抗原,这些抗原在宿主细胞表面表达。相比之下,很少有研究检测配子体感染红细胞的表面。
方法/主要发现:我们使用流式细胞术检测200名冈比亚儿童血浆中识别感染恶性疟原虫3D7株配子体的活培养红细胞表面的抗体。大多数儿童在疟疾治疗后被确定携带配子体,并且每人都献血用于蚊虫叮咬实验。没有一份血浆能识别感染配子体发育阶段(I-IV)的红细胞表面,但194份血浆中有66份(34.0%)含有能识别感染成熟(V期)配子体的红细胞表面的IgG。200份检测血浆中有34份(17.0%)能识别感染滋养体和裂殖体的红细胞,但这与识别配子体感染红细胞表面并无关联(优势比1.08,95%置信区间0.434 - 2.57;P = 0.851)。具有识别配子体表面抗原(GSA)能力的血浆抗体与识别配子抗原Pfs 230的抗体存在相关,但与Pfs48/45无关。识别GSA的抗体与抗疟治疗4周后配子体密度较低的献血者相关。
结论/意义:我们提供证据表明GSA与无性3D7寄生虫表面检测到的抗原不同。我们的发现为开发传播阻断疫苗提出了一种新策略。