Parasite load stemming from immunization route determines the duration of liver‐stage immunity

Abstract

Summary 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 TRAP130 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.

Infectious sporozoite challenge modulates radiation attenuated sporozoite vaccine–induced memory CD8+T cells for better survival characteristics

“…[5][6][7] Interestingly, an intermittent infectious sporozoite (SPZ) challenge to RAS-vaccinated mice has been shown to lengthen the protection period beyond 18 months. 6,[8][9][10][11][12] Therefore, studying the changes that infectious SPZ brought in RAS vaccine-induced CD8 + T cells would be important for designing an effective malaria vaccine.…”

Dissection-independent production ofPlasmodiumsporozoites from whole mosquitoes

“…Interestingly, recent work has shown intradermal immunisation with SGD-RASv was also associated with reduced efficacy compared with i.v. when challenged intradermally ( 59 ). Further work testing doses of sporozoites between MAF and SGD will be required to accurately assess comparative immunogenicity of different sporozoite sources and routes of immunisation.…”

Co-immunization with pre-erythrocytic antigens alongside circumsporozoite protein can enhance sterile protection against Plasmodium sporozoite infection.

“…The parasite load in the liver was determined as described previously 55 . Briefly, the livers were perfused 45 hr post mosquito-bite challenge with 1x PBS and total RNA was extracted from the lower right caudate process of the caudate lobe of the liver from each mouse using miRNeasy kit (Qiagen: 217004).…”