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. 2024 Mar 21;16(4):723–754. doi: 10.1038/s44321-024-00057-7

Figure 3. PyLARC2 immunization confers broad protection against sporozoite challenge and confers protection against blood stage challenge.

Figure 3

(A) Groups of outbred SW mice were immunized and challenged as shown in the schematic. The survival curve shows the percentage of mice that did not show blood stage parasites by thin blood smear, up to 21 days after sporozoite challenge. Seven of ten mice immunized with PyLARC2 were protected from challenge, while the three mice that developed blood stage parasitemia showed a 1-day delay in time to patency. All the naive and mock-immunized mice developed blood stage parasitemia 4 days after challenge. (B) Groups of BALB/cJ mice were immunized and challenged as shown in the schematic. The survival curve shows the percentage of mice that did not show blood stage parasites by thin blood smear, up to 21 days after sporozoite challenge. All twelve mice immunized with cryopreserved PyLARC2 were protected from challenge. All six naive mice developed blood stage parasitemia 5 days after challenge. (C) Stage transcending protection of PyLARC2 pre-erythrocytic immunization was evaluated as shown in the schematic by immunizing groups of BALB/c mice, followed by an intravenous challenge with 10,000 lethal Py XL infected RBCs (iRBC). All the naive and mock-immunized mice developed parasitemias exceeding 30% after 7 days of iRBC inoculation and had to be euthanized. All ten PyLARC2-immunized mice developed transient blood stage parasitemias up to 10% but cleared blood stage infection 12 days after challenge. Data is shown as mean ± SEM. Statistical analysis was carried out using two-way ANOVA using Tukey’s multiple comparison test. Comparison between mock and PyLARC2 immunized mice are shown in green stars and between naive and PyLARC2 immunized mice are shown in black stars. P values are indicated in the figure. P > 0.05 is taken as ns. (D) Protective efficacy of PyLARC2 immunization against a different Plasmodium species (P. berghei) was evaluated by immunizing groups of BALB/cJ mice as shown in the schematic. The survival curve shows the percentage of mice that did not show blood stage parasites by thin smear, up to 21 days after sporozoite challenge. All ten mice immunized with PyLARC2 were protected after challenge. All the naive and mock-immunized mice developed blood stage parasitemia 4 to 5 days after challenge. Source data are available online for this figure.