Biochemical Parasitology Unit, Institut Pasteur, Paris, France.
Malar J. 2009 Oct 29;8:247. doi: 10.1186/1475-2875-8-247.
A high level of genetic stability has been formerly identified in segments of the gene coding for the liver stage antigen-3 (LSA-3), a subunit vaccine candidate against Plasmodium falciparum. The exploration of lsa-3 polymorphisms was extended to the whole sequence of this large antigen in 20 clinical isolates from four geographical areas; Senegal, Comoro islands, Brazil and Thailand.
The whole 4680 bp genomic sequence of lsa-3 was amplified by polymerase chain reaction and sequenced. The clinical isolate sequences were aligned on the sequence of the laboratory reference P. falciparum strain 3D7.
The non-repeated sequence of lsa-3 was very well conserved with only a few allelic variations scattered along the sequence. Interestingly, a formerly identified immunodominant region, employed for the majority of pre-clinical vaccine development, was totally conserved at the genetic level. The most significant variations observed were in the number and organization of tetrapeptide repeated units, but not in their composition, resulting in different lengths of these repeated regions. The shorter repeated regions were from Brazilian origin. A correlation between the geographical distribution of the parasites with single nucleotide polymorphisms was not detected.
The lack of correlation between allelic polymorphisms with a specific transmission pressure suggests that LSA-3 is a structurally constrained molecule. The unusual characteristics of the lsa-3 gene make the molecule an interesting candidate for a subunit vaccine against malaria.
先前已鉴定出编码肝期抗原-3（LSA-3）的基因片段具有高水平的遗传稳定性，LSA-3 是一种针对恶性疟原虫的亚单位候选疫苗。在来自塞内加尔、科摩罗群岛、巴西和泰国四个地区的 20 个临床分离株中，对 lsa-3 多态性进行了扩展研究。
通过聚合酶链反应扩增了 lsa-3 的全长 4680 bp 基因组序列，并对其进行测序。将临床分离株序列与实验室参考株 3D7 的序列进行比对。
lsa-3 的非重复序列非常保守，只有少数等位基因变异散在整个序列中。有趣的是，以前鉴定的免疫显性区域被广泛用于大多数临床前疫苗开发，在遗传水平上完全保守。观察到的最显著变化是四肽重复单元的数量和组织，但它们的组成没有变化，导致这些重复区域的长度不同。较短的重复区域来自巴西。未检测到寄生虫的地理分布与单核苷酸多态性之间的相关性。
等位基因多态性与特定传播压力之间缺乏相关性表明，LSA-3 是一种结构受限的分子。lsa-3 基因的异常特征使该分子成为疟疾亚单位疫苗的一个有趣候选者。
