Adu Bright, Cherif Mariama K, Bosomprah Samuel, Diarra Amidou, Arthur Fareed K N, Dickson Emmanuel K, Corradin Giampietro, Cavanagh David R, Theisen Michael, Sirima Sodiomon B, Nebie Issa, Dodoo Daniel
Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana.
Polytechnic University of BoboDioulasso, Bobo-Dioulasso, Burkina Faso.
Malar J. 2016 Feb 27;15:123. doi: 10.1186/s12936-016-1146-4.
Differences in parasite transmission intensity influence the process of acquisition of host immunity to Plasmodium falciparum malaria and ultimately, the rate of malaria related morbidity and mortality. Potential vaccines being designed to complement current intervention efforts therefore need to be evaluated against different malaria endemicity backgrounds.
The associations between antibody responses to the chimeric merozoite surface protein 1 block 2 hybrid (MSP1 hybrid), glutamate-rich protein region 2 (GLURP R2) and the peptide AS202.11, and the risk of malaria were assessed in children living in malaria hyperendemic (Burkina Faso, n = 354) and hypo-endemic (Ghana, n = 209) areas. Using the same reagent lots and standardized protocols for both study sites, immunoglobulin (Ig) M, IgG and IgG sub-class levels to each antigen were measured by ELISA in plasma from the children (aged 6-72 months). Associations between antibody levels and risk of malaria were assessed using Cox regression models adjusting for covariates.
There was a significant association between GLURP R2 IgG3 and reduced risk of malaria after adjusting age of children in both the Burkinabe (hazard ratio 0.82; 95 % CI 0.74-0.91, p < 0.0001) and the Ghanaian (HR 0.48; 95 % CI 0.25-0.91, p = 0.02) cohorts. MSP1 hybrid IgM was associated (HR 0.85; 95 % CI 0.73-0.98, p = 0.02) with reduced risk of malaria in Burkina Faso cohort while IgG against AS202.11 in the Ghanaian children was associated with increased risk of malaria (HR 1.29; 95 % CI 1.01-1.65, p = 0.04).
These findings support further development of GLURP R2 and MSP1 block 2 hybrid, perhaps as a fusion vaccine antigen targeting malaria blood stage that can be deployed in areas of varying transmission intensity.
疟原虫传播强度的差异会影响宿主获得对恶性疟原虫疟疾免疫力的过程,最终影响疟疾相关发病和死亡率。因此,旨在补充当前干预措施的潜在疫苗需要在不同疟疾流行程度背景下进行评估。
在疟疾高度流行地区(布基纳法索,n = 354)和低度流行地区(加纳,n = 209)生活的儿童中,评估对嵌合裂殖子表面蛋白1第2区杂交体(MSP1杂交体)、富含谷氨酸蛋白区域2(GLURP R2)和肽AS202.11的抗体反应与疟疾风险之间的关联。两个研究地点使用相同的试剂批次和标准化方案,通过酶联免疫吸附测定法(ELISA)测量儿童(6至72个月龄)血浆中针对每种抗原的免疫球蛋白(Ig)M、IgG和IgG亚类水平。使用调整协变量的Cox回归模型评估抗体水平与疟疾风险之间的关联。
在布基纳法索队列(风险比0.82;95%置信区间0.74 - 0.91,p < 0.0001)和加纳队列(风险比0.48;95%置信区间0.25 - 0.91,p = 0.02)中,调整儿童年龄后,GLURP R2 IgG3与疟疾风险降低之间存在显著关联。在布基纳法索队列中,MSP1杂交体IgM与疟疾风险降低相关(风险比0.85;95%置信区间0.73 - 0.98,p = 0.02),而加纳儿童中针对AS202.11的IgG与疟疾风险增加相关(风险比1.29;95%置信区间1.01 - 1.65,p = 0.04)。
这些发现支持进一步开发GLURP R2和MSP1第2区杂交体,或许作为一种针对疟疾血期的融合疫苗抗原,可部署在不同传播强度的地区。