Antibodies to a merozoite surface protein promote multiple invasion of red blood cells by malaria parasites
Antibodies to a merozoite surface protein promote multiple invasion of red blood cells by malaria parasites
复制标题
DOI：
10.1046/j.1365-3024.1999.00239.x
复制
发表时间：
1999-08-01
影响因子：
2.2
通讯作者：
Ramasamy, MS
中科院分区：
文献类型：
--
作者：
Ramasamy, R;Yasawardena, S;Ramasamy, MS
40-50 kDa裂殖子表面抗原（MSA 2）是用于疟疾疫苗的候选分子。利用PCR技术扩增恶性疟原虫3D 7株的MSA 2基因，并将其克隆到原核表达载体pGEX-3X中，获得MSA 2与日本血吸虫谷胱甘肽S-转移酶的融合蛋白。用重组融合蛋白免疫家兔。注射四次后，血清的蛋白质印迹和免疫荧光滴度为10（-6）。免疫血清和免疫球蛋白（IG）G、F（ab ′ 2）、F（ab），通过显微镜和[H-3]-次黄嘌呤掺入试验评价它们对体外3D 7寄生虫生长的影响。当以10%v/v血清或浓度高达200 μ g ml（-1）的免疫球蛋白制剂加入培养物中时，抗体并不显著抑制红细胞侵入和寄生虫生长。然而，在存在IgG或F（ab）2抗体而非F（ab）抗体的情况下，被多于一个裂殖子侵入的红细胞的比例显著增加。多重侵入归因于裂殖子通过二价抗体交联，附着并随后侵入同一红细胞。这些观察结果与寄生虫逃避宿主免疫应答和在疟疾疫苗中使用全长重组MSA 2蛋白有关。
The 40-50 kDa merozoite surface antigen (MSA2) is a candidate molecule for use in a malaria vaccine. The gene for MSA2 from the 3D7 isolate of Plasmodium falciparum was amplified by polymerase chain reaction and cloned into the bacterial expression vector pGEX-3X to obtain a fusion protein of MSA2 with Schistosoma japonicum glutathione S-transferase. The recombinant fusion protein was used to immunize rabbits. After four injections, the sera had Western blotting and immunofluorescence titres of 10(-6). immune sera, and immunoglobulin (Ig)G, F(ab)'(2), F(ab) prepared from the immune sera, were assessed for their effects on the growth of 3D7 parasites in vitro by microscopy and a [H-3]-hypoxanthine incorporation assay. The antibodies did not significantly inhibit red blood cell invasion and parasite growth when added to cultures as 10% v/v serum or as immunoglobulin preparations at concentrations up to 200 mu g ml(-1). However, in the presence of IgG or F(ab)'2, but not F(ab), antibodies to MSA2, the proportions of red blood cells invaded by more than one merozoite increased significantly. Multiple invasion is attributed to merozoites cross-linked by bivalent antibodies, attaching to and subsequently invading the same red cell. These observations have a bearing on the evasion of host immune responses by the parasite and the use of full-length recombinant MSA2 protein in a malaria vaccine.