Induction of protective immunity in cattle against infection with Fasciola hepatica by vaccination with cathepsin L proteinases and with hemoglobin
Induction of protective immunity in cattle against infection with Fasciola hepatica by vaccination with cathepsin L proteinases and with hemoglobin
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DOI：
10.1128/iai.64.12.5066-5074.1996
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发表时间：
1996-12-01
影响因子：
3.1
通讯作者：
Andrews, SJ
中科院分区：
文献类型：
--
作者：
Dalton, JP;McGonigle, S;Andrews, SJ
肝吸虫分泌的两种组织蛋白酶 L1 和组织蛋白酶 L2 可能参与组织穿透、营养和免受免疫攻击的保护。为了确定这些蛋白酶和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。在第一次疫苗试验中，测试了不同剂量的组织蛋白酶 LI。获得的平均保护水平为 53.7%。在第二项疫苗试验中，组织蛋白酶 L1 和 Hb 分别产生了 42.5% 和 43.8% 的保护水平，而两种分子的组合则产生了显着更高的保护水平 (51.9%)。没有单独检查组织蛋白酶 L2；然而，用组织蛋白酶 L2 和 Hb 组合疫苗对牛进行疫苗接种可产生最高水平的保护（72.4%）。根据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 的动物可减轻肝损伤。此外，观察到从所有疫苗组中回收的吸虫卵的活力降低。疫苗接种的这种抗胚胎效应在接受组织蛋白酶 L2-Hb 的组中尤其明显，其中 > 98% 的回收卵子未胚胎发育为毛蚴。尽管所有疫苗制剂都会诱导高抗体滴度，并且在攻击感染后抗体滴度会升高，但抗体滴度和保护之间没有相关性。这些试验的结果表明，组织蛋白酶 Ls 和 Hb 可以构成分子疫苗的基础，该疫苗不仅可以减少寄生虫负担，还可以预防肝吸虫病的传播。
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 LI 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 shelved 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.