Checa Jackeline, Goyeche Antonella, Vettorazzi Renzo, Alonzo Pablo, Correa Oscar, Norbis Walter, Castillo Estela, Cancela Martin, Rossi Andrea, Silveira Fernando, Maggioli Gabriela
Laboratorio de Biología Parasitaria, Instituto de Higiene-Facultad de Ciencias, Universidad de la República, Av. Dr Alfredo Navarro, Montevideo 11600, Uruguay.
Campo Experimental, Instituto de Higiene, Universidad de la República, Canelones 46500, Uruguay.
Vaccines (Basel). 2025 Sep 26;13(10):1008. doi: 10.3390/vaccines13101008.
causes important economic losses in ruminants with only pharmacological treatments currently available, which produces several secondary problems. Because of this, vaccines have become an interesting alternative. Leucine aminopeptidases (LAPs) are attractive vaccine targets against fasciolosis since they play essential roles in the parasite such as host invasion and nutrient acquisition. To characterize immune responses, we produced two recombinant LAPs (LAP1 and LAP2), formulated with ISCOM-matrices (IMXs) nanoparticles from saponins. Forty female Corriedale sheep were assigned to four groups ( = 10): LAP1/IMX, LAP1/LAP2/IMX, IMX (control), and LAP1/Adj50 (Adjuvac 50). Animals received two subcutaneous immunizations at weeks 0 and 4 and were challenged orally with 200 metacercariae at week 6. LAP1 and LAP1/LAP2 induced specific IgG responses, with the predominance of the IgG1 response. However, these responses were lower than those generated by LAP1 formulated with Adj50. A qPCR analysis revealed that LAP1/IMX stimulated a Th1-type response profile before the challenge, but this profile was not sustained after infection. The post-infection profile of LAP1/LAP2/IMX was more congruent with expected values despite not achieving a robust IFN-γ expression. No significant differences in the fluke burden were observed. Further research on the optimal antigen/adjuvant combination in ruminants is encouraged. For instance, a higher concentration of adjuvant in the formulation used in this work may enhance the strength and duration of the inflammatory response and improve protective immunity against fasciolosis.
目前，在反刍动物中，该病仅通过药物治疗会造成重大经济损失，且会产生一些继发问题。因此，疫苗已成为一种有吸引力的替代方案。亮氨酸氨肽酶（LAPs）是抗片形吸虫病有吸引力的疫苗靶点，因为它们在寄生虫的宿主入侵和营养获取等过程中发挥着重要作用。为了表征免疫反应，我们制备了两种重组LAPs（LAP1和LAP2），并用来自皂苷的免疫刺激复合物基质（IMXs）纳米颗粒进行配制。将40只雌性考力代绵羊分为四组（每组 = 10只）：LAP1/IMX组、LAP1/LAP2/IMX组、IMX组（对照组）和LAP1/Adj50组（佐剂50组）。动物在第0周和第4周接受两次皮下免疫，并在第6周口服200个囊蚴进行攻毒。LAP1和LAP1/LAP2诱导了特异性IgG反应，其中以IgG1反应为主。然而，这些反应低于用Adj50配制的LAP1所产生的反应。定量聚合酶链反应（qPCR）分析显示，LAP1/IMX在攻毒前刺激了Th1型反应谱，但感染后该反应谱未持续。LAP1/LAP2/IMX感染后的反应谱与预期值更相符，尽管未实现强大的干扰素-γ（IFN-γ）表达。在吸虫负荷方面未观察到显著差异。鼓励对反刍动物中最佳抗原/佐剂组合进行进一步研究。例如，本研究中所用制剂中更高浓度的佐剂可能会增强炎症反应的强度和持续时间，并提高抗片形吸虫病的保护性免疫力。
