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

Vaccine. 2023 Jan 16:S0264-410X(23)00003-8. doi: 10.1016/j.vaccine.2023.01.004. Online ahead of print.ABSTRACTGenetically-growth-attenuated blood-stage parasites were generated inPlasmodium falciparumby targeted deletion of NT1 (Nucleoside Transporter-1) gene, and Pfnt1(-) parasites only grew after providing the culture with supra-physiological concentrations of purines. Genetically-attenuatedP. yoeliint1(-)parasites induced sterile-protection against homologous blood-stage infectious challenge after immunization with single subpatent doses, which remained subpatent even in immune-compromised mice. Here, we showed that immunizations with frozen-stocks of equally-mixedP. bergheiandP. yoelii nt1(-)parasites in single subcutaneous doses, which did not lead to patent blood-stage infection, conferred sterile protection against intravenous infectious blood-stage challenge with wild-type parasites ofP. bergheiANKA andP. yoelii17X-NL 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 twoPlasmodiumspp. infections, could be developed in cultures provided with supra-physiological concentrations of purines, and shipped to endemic areas as frozen-stock doses.PMID:36653222 | DOI:10.1016/j.vaccine.2023.01.004
Source: Vaccine - Category: Allergy & Immunology Authors: Source Type: research