Institute of Science, Nirma University, Ahmedabad, India.
Department of Cellular Immunology, Malaria Vaccine Branch, Walter Reed Army Institute of Research, Silver Spring, Maryland.
Parasite Immunol. 2019 Jul;41(7):e12622. doi: 10.1111/pim.12622. Epub 2019 Apr 4.
Immunization with radiation-attenuated Plasmodium sporozoites (RAS) induces sterile and long-lasting protective immunity. Although intravenous (IV) route of RAS immunization is reported to induce superior immunity compared to intradermal (ID) injection, its role in the maintenance of sterile immunity is yet to be understood. We investigated whether the route of homologous sporozoite challenge of Plasmodium berghei (Pb) RAS-immunized mice would influence the longevity of protection. C57BL/6 mice immunized with Pb-RAS by IV were 100% protected upon primary IV/ID sporozoite challenge. In contrast, ID immunization resulted in 80% protection, regardless of primary challenge route. Interestingly, the route of primary challenge was found to bring difference in the maintenance of sterile protection. While IV Pb RAS-immunized mice remained protected at all challenges regardless of the route of primary challenge, ID Pb-RAS-immunized mice receiving ID primary challenge became parasitaemic upon secondary IV challenge. Significantly, primary IV challenge of Pb RAS ID-immunized mice resulted in 80% and 50% survival at secondary and tertiary challenges, respectively. According to phenotypically diverse liver CD8 T cells, the percentages and the numbers of both CD8 T effector memory and resident memory cells were significantly higher in IV than in ID Pb RAS-immunized mice. IFN-γ-producing CD8 T cells specific to Pb TRAP and MIP-4-Kb-17 were also found significantly higher in IV mice than in ID mice. The enhanced T-cell generation and the longevity of protection appear to be dependent on the parasite load during challenge when infection is tolerated under suboptimal CD8 T-cell response.
用减毒疟原虫孢子（RAS）免疫可诱导无菌和持久的保护性免疫。虽然静脉（IV）途径的 RAS 免疫比皮内（ID）注射诱导更好的免疫，但它在维持无菌免疫中的作用尚不清楚。我们研究了 Plasmodium berghei（Pb）RAS 免疫小鼠同源孢子挑战的途径是否会影响保护的持久性。通过 IV 途径用 Pb-RAS 免疫的 C57BL/6 小鼠在初次 IV/ID 孢子挑战时 100%受到保护。相比之下，ID 免疫导致 80%的保护，无论初次挑战途径如何。有趣的是，初次挑战途径发现会对无菌保护的维持产生差异。虽然 IV Pb RAS 免疫的小鼠在所有挑战中均保持保护，无论初次挑战途径如何，但接受 ID 初次挑战的 ID Pb-RAS 免疫的小鼠在第二次 IV 挑战时出现寄生虫血症。重要的是，ID 初次挑战的 Pb RAS ID 免疫的小鼠在第二次和第三次挑战中分别有 80%和 50%的存活率。根据表型不同的肝 CD8 T 细胞，IV 比 ID Pb RAS 免疫的小鼠中 CD8 T 效应记忆和驻留记忆细胞的百分比和数量明显更高。针对 Pb TRAP 和 MIP-4-Kb-17 的 IFN-γ产生 CD8 T 细胞也在 IV 小鼠中明显高于 ID 小鼠。T 细胞的生成增强和保护的持久性似乎依赖于挑战时的寄生虫负荷，当感染在 CD8 T 细胞反应不佳的情况下耐受时。
