Dalton J P, McGonigle S, Rolph T P, Andrews S J
School of Biological Sciences, Dublin City University, Republic of Ireland.
Infect Immun. 1996 Dec;64(12):5066-74. doi: 10.1128/iai.64.12.5066-5074.1996.
Two cathepsin L proteinases, cathepsin L1 and cathepsin L2, secreted by liver flukes may be involved in tissue penetration, nutrition, and protection from immune attack. To ascertain the immunoprophylactic potential of these proteinases, and of another molecule, liver fluke hemoglobin (Hb), we performed vaccine trials in cattle. In the first vaccine trial various doses of cathepsin L1 were tested. The mean protection level obtained was 53.7%. In a second vaccine trial cathepsin L1 and Hb elicited 42.5 and 43.8% protection levels, respectively, while a combination of the two molecules induced a significantly higher level of protection (51.9%). Cathepsin L2 was not examined alone; however, vaccination of cattle with a combination of cathepsin L2 and Hb elicited the highest level of protection (72.4%). The animals that received cathepsin L1-Hb or cathepsin L2-Hb showed reduced liver damage as assessed by serum glutamic dehydrogenase and gamma-glutamyl transferase levels. Furthermore, a reduced viability was observed for fluke eggs recovered from all vaccine groups. This anti-embryonation effect of vaccination was particularly evident in the group that received cathepsin L2-Hb where >98% of the eggs recovered did not embryonate to miracidia. Although all vaccine preparations induced high antibody titers which were boosted following the challenge infection, there was no correlation between antibody titers and protection. The results of these trials demonstrate that cathepsin Ls and Hb could form the basis of a molecular vaccine that would not only reduce parasite burden but would also prevent transmission of liver fluke disease.
肝吸虫分泌的两种组织蛋白酶L蛋白酶,即组织蛋白酶L1和组织蛋白酶L2,可能参与组织穿透、营养摄取以及抵御免疫攻击的过程。为确定这些蛋白酶以及另一种分子——肝吸虫血红蛋白(Hb)的免疫预防潜力,我们在牛身上进行了疫苗试验。在首次疫苗试验中,测试了不同剂量的组织蛋白酶L1。获得的平均保护水平为53.7%。在第二次疫苗试验中,组织蛋白酶L1和Hb分别引发了42.5%和43.8%的保护水平,而这两种分子的组合诱导出了显著更高的保护水平(51.9%)。未单独检测组织蛋白酶L2;然而,用组织蛋白酶L2和Hb的组合对牛进行疫苗接种引发了最高的保护水平(72.4%)。通过血清谷氨酸脱氢酶和γ-谷氨酰转移酶水平评估,接受组织蛋白酶L1-Hb或组织蛋白酶L2-Hb的动物肝脏损伤减轻。此外,从所有疫苗组回收的吸虫卵活力降低。疫苗接种的这种抗胚胎发育作用在接受组织蛋白酶L2-Hb的组中尤为明显,该组中回收的卵>98%未发育成毛蚴。尽管所有疫苗制剂都诱导产生了高抗体滴度,且在攻击感染后抗体滴度有所提高,但抗体滴度与保护之间没有相关性。这些试验结果表明,组织蛋白酶L和Hb可构成分子疫苗的基础,这种疫苗不仅能减轻寄生虫负担,还能预防肝吸虫病的传播。