Population Health and Immunity Division, Walter and Eliza Hall Institute, Parkville, VIC, Australia.
Department of Medical Biology, University of Melbourne, Melbourne, VIC, Australia.
Malar J. 2017 Sep 25;16(1):386. doi: 10.1186/s12936-017-2042-2.
Further reduction in malaria prevalence and its eventual elimination would be greatly facilitated by the development of biomarkers of exposure and/or acquired immunity to malaria, as well as the deployment of effective vaccines against Plasmodium falciparum and Plasmodium vivax. A better understanding of the acquisition of immunity in naturally-exposed populations is essential for the identification of antigens useful as biomarkers, as well as to inform rational vaccine development.
ELISA was used to measure total IgG to a synthetic form of glycosylphosphatidylinositol from P. falciparum (PfGPI) in a cohort of 1-3 years old Papua New Guinea children with well-characterized individual differences in exposure to P. falciparum and P. vivax blood-stage infections. The relationship between IgG levels to PfGPI and measures of recent and past exposure to P. falciparum and P. vivax infections was investigated, as well as the association between antibody levels and prospective risk of clinical malaria over 16 months of follow-up.
Total IgG levels to PfGPI were low in the young children tested. Antibody levels were higher in the presence of P. falciparum or P. vivax infections, but short-lived. High IgG levels were associated with higher risk of P. falciparum malaria (IRR 1.33-1.66, P = 0.008-0.027), suggesting that they are biomarkers of increased exposure to P. falciparum infections. Given the cross-reactive nature of antibodies to PfGPI, high IgG levels were also associated with reduced risk of P. vivax malaria (IRR 0.65-0.67, P = 0.039-0.044), indicating that these antibodies are also markers of acquired immunity to P. vivax.
This study highlights that in young children, IgG to PfGPI might be a useful marker of immune-status to both P. falciparum and P. vivax infections, and potentially useful to help malaria control programs to identify populations at-risk. Further functional studies are necessary to confirm the potential of PfGPI as a target for vaccine development.
通过开发暴露和/或获得性疟疾免疫的生物标志物，以及部署针对恶性疟原虫和间日疟原虫的有效疫苗，将极大地促进疟疾发病率的进一步降低和最终消除。更好地了解自然暴露人群中免疫的获得情况，对于鉴定可用作生物标志物的抗原以及为合理的疫苗开发提供信息至关重要。
在巴布亚新几内亚的一个队列中，使用 ELISA 法测量了 1-3 岁儿童对恶性疟原虫糖基磷脂酰肌醇（PfGPI）的合成形式的总 IgG，该队列中儿童对恶性疟原虫和间日疟原虫血期感染的暴露存在明显差异。研究了 PfGPI 的 IgG 水平与近期和过去恶性疟原虫和间日疟原虫感染的关系，以及抗体水平与 16 个月随访期间临床疟疾的前瞻性风险之间的关系。
在接受测试的幼儿中，PfGPI 的总 IgG 水平较低。存在恶性疟原虫或间日疟原虫感染时，抗体水平较高，但持续时间较短。高水平的 IgG 与更高的恶性疟原虫疟疾风险相关（IRR 1.33-1.66，P=0.008-0.027），表明它们是恶性疟原虫感染暴露增加的生物标志物。鉴于 PfGPI 抗体的交叉反应性，高水平的 IgG 也与间日疟原虫疟疾的风险降低相关（IRR 0.65-0.67，P=0.039-0.044），表明这些抗体也是间日疟原虫获得性免疫的标志物。
本研究表明，在幼儿中，PfGPI 的 IgG 可能是恶性疟原虫和间日疟原虫感染免疫状态的有用标志物，可能有助于疟疾控制计划识别高危人群。需要进一步的功能研究来确认 PfGPI 作为疫苗开发目标的潜力。
