Flück Christian, Smith Tom, Beck Hans-Peter, Irion Andrea, Betuela Inoni, Alpers Michael P, Anders Robin, Saul Allan, Genton Blaise, Felger Ingrid
Swiss Tropical Institute, Socinstrasse 57, Basel.
Infect Immun. 2004 Nov;72(11):6300-5. doi: 10.1128/IAI.72.11.6300-6305.2004.
The 3D7 form of the merozoite surface protein 2 (MSP2) of Plasmodium falciparum was one of three subunits of the malaria vaccine Combination B that were tested in a phase I/IIb double-blind randomized placebo-controlled trial, which was undertaken with 120 Papua New Guinean children of 5 to 9 years of age. Because only one variant of the highly polymorphic MSP2 was used for vaccination, we examined whether the elicited response was directed against conserved or strain-specific epitopes. Postvaccination (week 12) titers of antibody against recombinantly expressed individual domains of MSP2 were measured by enzyme-linked immunosorbent assay and compared to baseline values. We found that vaccination with the 3D7 form of MSP2 induced a significant strain-specific humoral response directed against the repetitive and semiconserved family-specific part. The conserved N- and C-terminal domains were not immunogenic. Titers of antibody against the alternate FC27 family-specific domain showed a tendency to increase in vaccinated children, but there was no increase in antibodies against FC27-type 32-mer repeats. These results indicate that vaccination with one MSP2 variant mainly induced a strain-specific response, which can explain the selective effect of vaccination with combination B on the genotypes of breakthrough parasites. These findings support the inclusion of both family-specific domains (3D7 and FC27) in an improved vaccine formulation.
恶性疟原虫裂殖子表面蛋白2（MSP2）的3D7形式是疟疾疫苗组合B的三个亚基之一，该疫苗在一项I/IIb期双盲随机安慰剂对照试验中进行了测试，试验对象为120名5至9岁的巴布亚新几内亚儿童。由于高度多态性的MSP2仅使用了一个变体进行疫苗接种，我们研究了引发的反应是针对保守表位还是菌株特异性表位。通过酶联免疫吸附测定法测量接种疫苗后（第12周）针对重组表达的MSP2各个结构域的抗体滴度，并与基线值进行比较。我们发现，用MSP2的3D7形式进行疫苗接种可诱导针对重复且半保守的家族特异性部分的显著菌株特异性体液反应。保守的N端和C端结构域没有免疫原性。针对替代的FC27家族特异性结构域的抗体滴度在接种疫苗的儿童中显示出增加的趋势，但针对FC27型32聚体重复序列的抗体没有增加。这些结果表明，用一种MSP2变体进行疫苗接种主要诱导了菌株特异性反应，这可以解释组合B疫苗接种对突破性寄生虫基因型的选择性作用。这些发现支持在改进的疫苗配方中同时包含家族特异性结构域（3D7和FC27）。
