Creation and preclinical evaluation of genetically attenuated malaria parasites arresting growth late in the liver.
Journal
NPJ vaccines
ISSN: 2059-0105
Titre abrégé: NPJ Vaccines
Pays: England
ID NLM: 101699863
Informations de publication
Date de publication:
04 Nov 2022
04 Nov 2022
Historique:
received:
23
03
2022
accepted:
13
10
2022
pubmed:
6
11
2022
medline:
6
11
2022
entrez:
5
11
2022
Statut:
epublish
Résumé
Whole-sporozoite (WSp) malaria vaccines induce protective immune responses in animal malaria models and in humans. A recent clinical trial with a WSp vaccine comprising genetically attenuated parasites (GAP) which arrest growth early in the liver (PfSPZ-GA1), showed that GAPs can be safely administered to humans and immunogenicity is comparable to radiation-attenuated PfSPZ Vaccine. GAPs that arrest late in the liver stage (LA-GAP) have potential for increased potency as shown in rodent malaria models. Here we describe the generation of four putative P. falciparum LA-GAPs, generated by CRISPR/Cas9-mediated gene deletion. One out of four gene-deletion mutants produced sporozoites in sufficient numbers for further preclinical evaluation. This mutant, PfΔmei2, lacking the mei2-like RNA gene, showed late liver growth arrest in human liver-chimeric mice with human erythrocytes, absence of unwanted genetic alterations and sensitivity to antimalarial drugs. These features of PfΔmei2 make it a promising vaccine candidate, supporting further clinical evaluation. PfΔmei2 (GA2) has passed regulatory approval for safety and efficacy testing in humans based on the findings reported in this study.
Identifiants
pubmed: 36333336
doi: 10.1038/s41541-022-00558-x
pii: 10.1038/s41541-022-00558-x
pmc: PMC9636417
doi:
Types de publication
Journal Article
Langues
eng
Pagination
139Informations de copyright
© 2022. The Author(s).
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