Bergmann-Leitner Elke S, Duncan Elizabeth H, Angov Evelina
US Military Malaria Vaccine Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
Malar J. 2009 Aug 3;8:183. doi: 10.1186/1475-2875-8-183.
Antibodies are the main effector molecules in the defense against blood stages of the malaria parasite Plasmodium falciparum. Understanding the mechanisms by which vaccine-induced anti-blood stage antibodies work in protecting against malaria is essential for vaccine design and testing.
The effects of MSP-1p42-specific antibodies on the development of blood stage parasites were studied using microscopy, flow cytometry and the pLDH assay. To determine allele-specific effects, if present, allele-specific antibodies and the various parasite clones representative of these alleles of MSP-1 were employed.
The mode of action of anti-MSP-1p42 antibodies differs among the parasite clones tested: anti-MSP-1p42 sera act mainly through invasion-inhibitory mechanisms against FVO parasites, by either preventing schizonts from rupturing or agglutinating merozoites upon their release. The same antibodies do not prevent the rupture of 3D7 schizonts; instead they agglutinate merozoites and arrest the development of young parasites at the early trophozoite stage, thus acting through both invasion- and growth inhibitory mechanisms. The second key finding is that antibodies have access to the intra-erythrocytic parasite, as evidenced by the labeling of developing merozoites with fluorochrome-conjugated anti-MSP-1p42 antibodies. Access to the parasite through this route likely allows antibodies to exert their inhibitory activities on the maturing schizonts leading to their inability to rupture and be released as infectious merozoites.
The identification of various modes of action by which anti-MSP-1 antibodies function against the parasite during erythrocytic development emphasizes the importance of functional assays for evaluating malaria vaccines and may also open new avenues for immunotherapy and vaccine development.
抗体是抵御恶性疟原虫血液阶段的主要效应分子。了解疫苗诱导的抗血液阶段抗体预防疟疾的作用机制对于疫苗设计和测试至关重要。
使用显微镜、流式细胞术和pLDH测定法研究了MSP-1p42特异性抗体对血液阶段寄生虫发育的影响。为了确定等位基因特异性效应（如果存在），使用了等位基因特异性抗体和代表MSP-1这些等位基因的各种寄生虫克隆。
抗MSP-1p42抗体的作用模式在测试的寄生虫克隆中有所不同：抗MSP-1p42血清主要通过针对FVO寄生虫的入侵抑制机制起作用，要么阻止裂殖体破裂，要么在裂殖子释放时使其凝集。相同的抗体不会阻止3D7裂殖体的破裂；相反，它们会凝集裂殖子并在滋养体早期阶段阻止年轻寄生虫的发育，从而通过入侵抑制和生长抑制机制起作用。第二个关键发现是抗体能够进入红细胞内的寄生虫，用荧光染料偶联的抗MSP-1p42抗体标记发育中的裂殖子就证明了这一点。通过这条途径进入寄生虫可能使抗体对成熟裂殖体发挥抑制活性，导致其无法破裂并释放出具有感染性的裂殖子。
抗MSP-1抗体在红细胞发育过程中对寄生虫发挥作用的各种作用模式的鉴定强调了功能测定在评估疟疾疫苗中的重要性，也可能为免疫治疗和疫苗开发开辟新途径。
