Studies in animal models suggest that protection against malaria induced by intradermal (ID) administration of sporozoites is less effective compared to intravenous injection (IV). We investigated in a murine model the protective efficacy and immune responses after ID or IV immunization of sporozoites. Mice were immunized via either IV or ID route with P. berghei sporozoites in combination with chloroquine treatment (CPS) (allowing full liver stage development) or by γ-radiation attenuated sporozoites (RAS) (early liver stage arrest). While IV immunization with both RAS and CPS generated 90-100% protection, ID immunization resulted in reduced levels of protection with either immunization strategy in both Balb/cByJ (50%) and C57BL/6j mice (7-13%). Lower protection by ID routing associated with a 30-fold lower parasite liver load (p<0.001 (χ²= 49.08, (df 1)) assessed by real time in vivo imaging of bioluminescent P. berghei parasites. Unlike IV, ID immunization did not result in expansion of CD8+ T-cells with effector memory phenotype and showed lower IFNγ responses irrespective of the immunization regime. In conclusion, protection against sporozoite infection is likely dependent on parasite liver infection and subsequently generated cellular immune responses.

中文翻译：

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减少伯氏疟原虫子孢子肝负荷与皮内免疫后保护功效低有关

动物模型研究表明，与静脉注射 (IV) 相比，皮内 (ID) 给予子孢子对疟疾的保护效果较差。我们在小鼠模型中研究了子孢子 ID 或 IV 免疫后的保护效力和免疫反应。用伯氏疟原虫通过 IV 或 ID 途径免疫小鼠子孢子与氯喹治疗（CPS）（允许肝脏完全发育）或γ-辐射衰减子孢子（RAS）（早期肝脏阶段停滞）相结合。虽然 RAS 和 CPS 的 IV 免疫产生了 90-100% 的保护，但 ID 免疫导致 Balb/cByJ (50%) 和 C57BL/6j 小鼠 (7-13%) 中任一免疫策略的保护水平降低。通过生物发光P. berghei的实时体内成像评估，ID 路由的较低保护与 30 倍的寄生虫肝脏负荷 (p<0.001 (χ ^{2 = 49.08, (df 1)) 相关}寄生虫。与 IV 不同，ID 免疫不会导致具有效应记忆表型的 CD8+ T 细胞扩增，并且无论免疫方案如何，都显示出较低的 IFNγ 反应。总之，对子孢子感染的保护可能取决于寄生虫肝脏感染并随后产生细胞免疫反应。