Holder A A, Guevara Patiño J A, Uthaipibull C, Syed S E, Ling I T, Scott-Finnigan T, Blackman M J
Division of Parasitology, National Institute for Medical Research, London, UK.
Parassitologia. 1999 Sep;41(1-3):409-14.
There is an urgent need for a vaccine against malaria and proteins on the surface of the merozoite are good targets for development as vaccine candidates because they are exposed to antibody. However, it is possible that the parasite has evolved mechanisms to evade a protective immune response to these proteins. Merozoite surface protein 1 (MSP-1) is a candidate for vaccine development and its C-terminal sequence is the target of protective antibody. MSP-1 is cleaved by proteases in two processing steps, the second step releases the bulk of the protein from the surface and goes to completion during successful red blood cell invasion. Antibodies binding to the C-terminus of Plasmodium falciparum MSP-1 can inhibit both the processing and erythrocyte invasion. Other antibodies that bind to either the C-terminal sequence or elsewhere in the molecule are 'blocking' antibodies, which on binding prevent the binding of the inhibitory antibodies. Blocking antibodies are a mechanism of immune evasion, which may be based on antigenic conservation rather than diversity. This mechanism has a number of implications for the study of protective immunity and the development of malaria vaccines, emphasising the need for appropriate functional assays and careful design of the antigen.
迫切需要一种抗疟疾疫苗，而裂殖子表面的蛋白质是作为候选疫苗开发的良好靶点，因为它们会暴露于抗体。然而，寄生虫有可能已经进化出逃避针对这些蛋白质的保护性免疫反应的机制。裂殖子表面蛋白1（MSP-1）是疫苗开发的候选物，其C端序列是保护性抗体的靶点。MSP-1在两个加工步骤中被蛋白酶切割，第二步将大部分蛋白质从表面释放出来，并在成功侵入红细胞的过程中完成。与恶性疟原虫MSP-1的C端结合的抗体可以抑制加工过程和红细胞侵入。其他与C端序列或分子其他部位结合的抗体是“阻断”抗体，它们在结合时会阻止抑制性抗体的结合。阻断抗体是一种免疫逃避机制，其可能基于抗原保守性而非多样性。这种机制对保护性免疫的研究和疟疾疫苗的开发有许多影响，强调了进行适当功能测定和精心设计抗原的必要性。
