Creation and preclinical evaluation of genetically attenuated malaria parasites arresting growth late in the liver.

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)


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


500 Science > 570 Life sciences; biology




Nature Publishing Group




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Date Deposited:

07 Nov 2022 14:13

Last Modified:

02 Mar 2023 23:36

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