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

Genetically-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(-...

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Veröffentlicht in:Vaccine 2023-02, Vol.41 (7), p.1281-1285
Hauptverfasser: Deveci, Gozde, Kamil, Mohd, Aly, Ahmed S.I.
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Kamil, Mohd
Aly, Ahmed S.I.
description Genetically-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.
doi_str_mv 10.1016/j.vaccine.2023.01.004
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subjects Animals
Attenuation
Blood
Blood-stage vaccine
Frozen-stock
Gene deletion
genes
Genotype & phenotype
Humans
Immunization
Infections
Injections
intravenous injection
Malaria
Malaria Vaccines
Mice
Microscopy
Mixed immunization
Neurotrophin 1
Nucleoside transporter
nucleosides
Parasites
Physiology
Plasmodium
Plasmodium berghei
Plasmodium yoelii
Purines
species
Subcutaneous immunization
Vaccination
Vaccines
Vector-borne diseases
title A single dose of genetically-attenuated malaria blood-stage parasites protects against two Plasmodium species infections
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