Nawaratna Sujeevi S K, Gobert Geoffrey N, Willis Charlene, Mulvenna Jason, Hofmann Andreas, McManus Donald P, Jones Malcolm K
School of Veterinary Sciences, The University of Queensland, Gatton Campus, Gatton Qld, 4343, Australia.
QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, Qld, 4006, Australia.
Sci Rep. 2015 Oct 16;5:15069. doi: 10.1038/srep15069.
Our previously reported gene atlasing of schistosome tissues revealed transcripts that were highly enriched in the digestive tract of Schistosoma mansoni. From these, we selected two candidates, Sm-LAMP and Sm-NPC2 for testing as vaccine targets. The two molecules were selected on the basis of relatively high expression in the gastrodermis, their potentially important biological function, divergence from homologous molecules of the host and possible apical membrane expression in the gastrodermis. Bacterially expressed recombinant peptides corresponding to regions excluding trans-membrane domains of the selected vaccine targets were used in blinded vaccine trials in CBA mice using alum-CpG as adjuvant. Vaccine trials using the recombinant insoluble Sm-LAMP protein showed 16-25% significant reduction in total worm burden. Faecal egg count reduction was 52% and 60% in two trials, respectively, with similar results for the solubly expressed protein. Liver egg burden was reduced significantly (20% and 38%) with an insoluble recombinant Sm-LAMP in two trials, but not with the soluble recombinant form. Parasite fecundity was not affected by either Sm-LAMP protein preparations in the trials. It is concluded that Sm-LAMP may provide limited protection towards S. mansoni infections but could be used in combination with other vaccine candidates, to provide more comprehensive protection.
我们之前报道的血吸虫组织基因图谱揭示了在曼氏血吸虫消化道中高度富集的转录本。基于这些转录本,我们选择了两个候选分子,即Sm-LAMP和Sm-NPC2作为疫苗靶点进行测试。选择这两个分子是基于它们在胃皮层中相对较高的表达水平、潜在的重要生物学功能、与宿主同源分子的差异以及在胃皮层中可能的顶端膜表达。在使用明矾-甲基化CpG作为佐剂的CBA小鼠盲法疫苗试验中,使用了与所选疫苗靶点跨膜结构域以外区域相对应的细菌表达重组肽。使用重组不溶性Sm-LAMP蛋白的疫苗试验显示,总虫负荷显著降低了16%-25%。在两项试验中,粪便虫卵计数减少分别为52%和60%,可溶性表达蛋白的结果相似。在两项试验中,不溶性重组Sm-LAMP可使肝脏虫卵负荷显著降低(分别为20%和38%),但可溶性重组形式则无此效果。在试验中,两种Sm-LAMP蛋白制剂均未影响寄生虫的繁殖力。结论是,Sm-LAMP可能对曼氏血吸虫感染提供有限的保护,但可与其他疫苗候选物联合使用,以提供更全面的保护。