Franke-Fayard, Blandine; Marin-Mogollon, Catherin; Geurten, Fiona J A; Chevalley-Maurel, Séverine; Ramesar, Jai; Kroeze, Hans; Baalbergen, Els; Wessels, Els; Baron, Ludivine; Soulard, Valérie; Martinson, Thomas; Aleshnick, Maya; Huijs, Antonius T G; Subudhi, Amit K; Miyazaki, Yukiko; Othman, Ahmad Syibli; Kolli, Surendra Kumar; Lamers, Olivia A C; Roques, Magali; Stanway, Rebecca R; ... (2022). Creation and preclinical evaluation of genetically attenuated malaria parasites arresting growth late in the liver. npj vaccines, 7(1), p. 139. Nature Publishing Group 10.1038/s41541-022-00558-x
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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.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
05 Veterinary Medicine > Other Institutions > Centers Vetsuisse Faculty > Multidisciplinary Center for Infectious Diseases (MCID) 05 Veterinary Medicine > Other Institutions 08 Faculty of Science > Department of Biology > Institute of Cell Biology |
UniBE Contributor: |
Roques, Magali Hélène Yvonne, Limenitakis, Rebecca Rachel, Heussler, Volker |
Subjects: |
500 Science > 570 Life sciences; biology |
ISSN: |
2059-0105 |
Publisher: |
Nature Publishing Group |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
07 Nov 2022 14:13 |
Last Modified: |
02 Mar 2023 23:36 |
Publisher DOI: |
10.1038/s41541-022-00558-x |
PubMed ID: |
36333336 |
BORIS DOI: |
10.48350/174536 |
URI: |
https://boris.unibe.ch/id/eprint/174536 |
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