Zerna Gemma, Rathinasamy Vignesh A, Toet Hayley, Anderson Glenn, Dempster Robert, Spithill Terry W, Beddoe Travis
Department of Animal, Plant and Soil Sciences and Centre for AgriBioscience, La Trobe University, Bundoora, VIC 3083, Australia.
Intensive Livestock, Fisheries & Aquaculture Research, Development & Extension, Department of Agriculture and Fisheries, Dutton Park, QLD 4102, Australia.
Vaccines (Basel). 2021 Oct 20;9(11):1213. doi: 10.3390/vaccines9111213.
Fasciolosis, caused by the liver flukes and is an economically important and globally distributed zoonotic disease. Liver fluke infections in livestock cause significant losses in production and are of particular concern to regions where drug resistance is emerging. Antigens of the surface tegument represent promising vaccine candidates for controlling this disease. Tetraspanins are integral tegumental antigens that have shown partial protection as vaccine candidates against other trematode species. The heat-labile enterotoxin's B subunit (LTB) is a potent mucosal adjuvant capable of inducing an immune response to fused antigens. This study investigates the potential of tetraspanin 2 extracellular loop 2 (rFhTSP2) as a protective vaccine antigen and determines if fusion of FhTSP2 to LTB can enhance protection in cattle. Cattle were immunised subcutaneously with rFhTSP2 mixed in the Freund's adjuvant and intranasally with rLTB-FhTSP2 in saline, accounting for equal molar ratios of tetraspanin in both groups. Vaccination with rFhTSP2 stimulated a strong specific serum IgG response, whereas there was no significant serum IgG response following rLTB-FhTSP2 intranasal vaccination. There was no substantial antigen specific serum IgA generated in all groups across the trial. Contrastingly, after the fluke challenge, a rise in antigen specific saliva IgA was observed in both vaccination groups on Day 42, with the rLTB-FhTSP2 vaccination group showing significant mucosal IgA production at Day 84. However, neither vaccine group showed a significant reduction of fluke burden nor faecal egg output. These results suggest that intranasal vaccination with rLTB-FhTSP2 does elicit a humoral mucosal response but further work is needed to evaluate if mucosal delivery of liver fluke antigens fused to LTB is a viable vaccine strategy.
肝片吸虫病由肝吸虫引起，是一种具有重要经济意义且在全球范围内分布的人畜共患病。家畜感染肝吸虫会导致生产上的重大损失，在出现耐药性的地区尤其令人担忧。体表被膜抗原是控制这种疾病的有前景的疫苗候选物。四跨膜蛋白是完整的被膜抗原，作为针对其他吸虫物种的疫苗候选物已显示出部分保护作用。不耐热肠毒素的B亚基（LTB）是一种有效的黏膜佐剂，能够诱导对融合抗原的免疫反应。本研究调查了四跨膜蛋白2细胞外环2（rFhTSP2）作为保护性疫苗抗原的潜力，并确定FhTSP2与LTB融合是否能增强对牛的保护作用。牛分别皮下注射与弗氏佐剂混合的rFhTSP2，以及经鼻注射盐水中的rLTB-FhTSP2，两组中四跨膜蛋白的摩尔比相等。用rFhTSP2疫苗接种刺激了强烈的特异性血清IgG反应，而经鼻接种rLTB-FhTSP2后未出现显著的血清IgG反应。在整个试验中，所有组均未产生大量的抗原特异性血清IgA。相反，在吸虫攻击后，两个疫苗接种组在第42天均观察到抗原特异性唾液IgA升高，rLTB-FhTSP2疫苗接种组在第84天显示出显著的黏膜IgA产生。然而，两个疫苗组均未显示出吸虫负担或粪便虫卵产量的显著降低。这些结果表明，经鼻接种rLTB-FhTSP2确实会引发体液黏膜反应，但需要进一步研究来评估将与LTB融合的肝吸虫抗原进行黏膜递送是否是一种可行的疫苗策略。
