Subcutaneous Immunization with Unaltered Axenic Malaria Parasite Liver Stages Induces Sterile Protection against Infectious Sporozoite Challenge

Abstract

Host cell-free, axenic development of liver stages (LS) of the malaria parasite has been demonstrated. Here we explored axenic liver stages as a novel live whole parasite malaria vaccine platform, which is unaltered and not prone to human-error, compared to the immunization with live-attenuated sporozoites that must be done intravenously. We show that in contrast to live sporozoites, axenic LS are not infectious to the immunized host. Subcutaneous immunizations of mice with Plasmodium yoelii axenic LS, developed from wild-type (WT) sporozoites or WT sporozoites expressing enhanced-GFP, conferred sterile protection against P. yoelii infectious sporozoite challenge. Thus, axenic liver stages of P. falciparum and P. vivax might constitute an attractive alternative to live sporozoite immunization.

Endoplasmic reticulum localized TMEM33 domain‐containing protein is crucial for all life cycle stages of the malaria parasite

“…Mice were infected intraperitoneally with cryopreserved stocks of P. berghei WT, Pbp230p(−) , Pbtmem33(−) , and Pbtmem33‐mNG tag by. For mosquito infection, female Anopheles stephensi mosquitoes were blood‐fed on P. berghei ANKA WT, Pbp230p(−) , Pbtmem33(−) , and Pbtmem33‐mNG tagged parasite strains infected mice as described previously (Aly et al., 2019; Kamil, Deveci, et al., 2022).…”