A single dose of genetically-attenuated malaria blood-stage parasites protects against two Plasmodium species infections

Genetically-growth-attenuated blood-stage parasites were generated in Plasmodium falciparum by tar- geted deletion of NT1 (ucleoside Transporter-1) gene, and Pint1(-) parasites only grew after providing the culture with supra-physiological concentrations of purines. Genetically-attenuated P. yoeliitl(-) parasites induced steril-protection against homologous blood-stage infectious challenge after immu- nization with single subpatent doses, which remained subpatent even in immune-compromised mice. Here, we showed that imunizations with frozen-stocks of equally-mixed berghei and P. yoeliint(-) parasites in single subcutaneous doses, which did not lead to parent blood-stage infection, conferred ster- ile protection against Intravenous infectious blood-stage challenge with wild-type parasites of P berghel ANKA and P. yoelii 17X-NI. strains. This data highlights the possibility that a single subcutaneous sub-patent dose of two species of genetically-growth-attenuated parasites, which can protect humans against two Plasmodium spp. infections, could be developed in cultures provided with supra- physiological concentrations of purines, and shipped to endemic areas as frozen-stock doses. (c) 2023 Published by Elsevier Ltd.

Automated summary

Genetically-growth-attenuated blood-stage parasites were developed and shown to induce sterile protection against homologous blood-stage infection. Immunization with frozen stocks of mixed berghei and P. yoeliint(-) parasites in subcutaneous doses conferred sterile protection against intravenous infectious blood-stage challenge. This finding suggests the potential development of a single subcutaneous sub-patent dose of genetically-growth-attenuated parasites as a protective measure against multiple Plasmodium spp. infections.