Identification of protective peptides of Fasciola hepatica-derived cathepsin L1 (FhCL1) in vaccinated sheep by a linear B-cell epitope mapping approach
Identification of protective peptides of Fasciola hepatica-derived cathepsin L1 (FhCL1) in vaccinated sheep by a linear B-cell epitope mapping approach
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DOI：
10.1186/s13071-020-04260-6
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发表时间：
2020-07-31
影响因子：
3.2
通讯作者：
Mulcahy, Grace
中科院分区：
文献类型：
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作者：
Buffoni, Leandro;Garza-Cuartero, Laura;Mulcahy, Grace
肝片吸虫病是家畜的重要寄生虫病之一。由于需要更好的控制策略，因此需要确定各种候选疫苗。半胱氨酸蛋白酶家族成员肝片吸虫组织蛋白酶L1（FhCL 1）的重组形式在过去几十年中一直是疫苗靶点，因为它已被证明表现为免疫显性抗原。然而，当FhCL 1被用作疫苗时，已经观察到在一些试验中引起显著的保护，而在其他试验中没有提供保护。为了改进疫苗开发策略，我们在用FhCL 1、FhHDM、FhPrx和Montanide接种的绵羊中进行了FhCL 1的线性B细胞表位作图，并且在显著减少吸虫负担的情况下，用FhCL 1、FhHDM、结果我们的研究表明，肽识别的模式和动力学在两个接种组之间有明显变化，并且在前肽内的区域55-63和77-84，FhCL 1的102-114和265-273区域仅被免疫羊特异性识别，并显著降低了吸虫负担。此外，这些动物也表现出显着的生产特定的IgG 2，而没有观察到接种氢氧化铝和感染的control animals.ConclusionsWe已经确定了42个残基的FhCL 1，有助于保护性免疫对感染F。羊肝我们的研究结果提供了有关免疫反应的关键方面的迹象。鉴于迄今为止在反刍动物中进行的疫苗接种试验的结果不同，这项研究为改进疫苗开发策略提供了新的见解。
BackgroundFasciolosis is one of the most important parasitic diseases of livestock. The need for better control strategies gave rise to the identification of various vaccine candidates. The recombinant form of a member of the cysteine protease family, cathepsin L1 of Fasciola hepatica (FhCL1) has been a vaccine target for the past few decades since it has been shown to behave as an immunodominant antigen. However, when FhCL1 was used as vaccine, it has been observed to elicit significant protection in some trials, whereas no protection was provided in others.MethodsIn order to improve vaccine development strategy, we conducted a linear B-cell epitope mapping of FhCL1 in sheep vaccinated with FhCL1, FhHDM, FhLAP and FhPrx plus Montanide and with significant reduction of the fluke burden, sheep vaccinated with FhCL1, FhHDM, FhLAP and FhPrx plus aluminium hydroxide and with non-significant reduction of the fluke burden, and in unvaccinated-infected sheep.ResultsOur study showed that the pattern and dynamic of peptide recognition varied noticeably between both vaccinated groups, and that the regions 55-63 and 77-84, which are within the propeptide, and regions 102-114 and 265-273 of FhCL1 were specifically recognised only by vaccinated sheep with significant reduction of the fluke burden. In addition, these animals also showed significant production of specific IgG2, whereas none was observed in vaccinated-Aluminium hydroxide and in infected control animals.ConclusionsWe have identified 42 residues of FhCL1 that contributed to protective immunity against infection with F. hepatica in sheep. Our results provide indications in relation to key aspects of the immune response. Given the variable outcomes of vaccination trials conducted in ruminants to date, this study adds new insights to improve strategies of vaccine development.