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

Autor: Franke-Fayard B; Malaria Research Group, Department of Parasitology, Leiden University medical Center, Leiden, The Netherlands. bfranke@lumc.nl., Marin-Mogollon C; Malaria Research Group, Department of Parasitology, Leiden University medical Center, Leiden, The Netherlands., Geurten FJA; Malaria Research Group, Department of Parasitology, Leiden University medical Center, Leiden, The Netherlands., Chevalley-Maurel S; Malaria Research Group, Department of Parasitology, Leiden University medical Center, Leiden, The Netherlands., Ramesar J; Malaria Research Group, Department of Parasitology, Leiden University medical Center, Leiden, The Netherlands., Kroeze H; Malaria Research Group, Department of Parasitology, Leiden University medical Center, Leiden, The Netherlands., Baalbergen E; Malaria Research Group, Department of Parasitology, Leiden University medical Center, Leiden, The Netherlands., Wessels E; Department of Medical Microbiology, Leiden University Medical Center, 2300 RC, Leiden, the Netherlands., Baron L; Sorbonne Université, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National pour la Recherche Scientifique (CNRS), Centre d'Immunologie et des Maladies Infectieuses, CIMI, Paris, France., Soulard V; Sorbonne Université, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National pour la Recherche Scientifique (CNRS), Centre d'Immunologie et des Maladies Infectieuses, CIMI, Paris, France., Martinson T; Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR, 97006, USA., Aleshnick M; Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR, 97006, USA., Huijs ATG; TropIQ Health Sciences, Nijmegen, the Netherlands., Subudhi AK; Pathogen Genomics Laboratory, Biological and Environmental Sciences and Engineering (BESE) Division, King Abdullah University of Science and Technology (KAUST), Thuwal, Kingdom of Saudi Arabia., Miyazaki Y; Malaria Research Group, Department of Parasitology, Leiden University medical Center, Leiden, The Netherlands.; Department of Cellular Architecture Studies, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan., Othman AS; Universiti Sultan Zainal Abidin, Faculty of Health Sciences, Terengganu, Malaysia., Kolli SK; Malaria Research Group, Department of Parasitology, Leiden University medical Center, Leiden, The Netherlands.; Center for Global Health and Infectious Diseases Research, College of Public Health, University of South Florida, Tampa, FL, USA., Lamers OAC; Malaria Research Group, Department of Parasitology, Leiden University medical Center, Leiden, The Netherlands., Roques M; Institute of Cell Biology, University of Bern, Bern, Switzerland., Stanway RR; Institute of Cell Biology, University of Bern, Bern, Switzerland.; Multidisciplinary Center for Infectious Diseases (MCID), University of Bern, Bern, Switzerland., Murphy SC; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA., Foquet L; Yecuris Corporation, Tualatin, OR, USA., Moita D; Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal., Mendes AM; Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal., Prudêncio M; Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal., Dechering KJ; TropIQ Health Sciences, Nijmegen, the Netherlands., Heussler VT; Institute of Cell Biology, University of Bern, Bern, Switzerland., Pain A; Pathogen Genomics Laboratory, Biological and Environmental Sciences and Engineering (BESE) Division, King Abdullah University of Science and Technology (KAUST), Thuwal, Kingdom of Saudi Arabia.; International Institute for Zoonosis Control, Hokkaido University, N20 W10 Kita-ku, Sapporo, Japan., Wilder BK; Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR, 97006, USA., Roestenberg M; Malaria Research Group, Department of Parasitology, Leiden University medical Center, Leiden, The Netherlands. M.Roestenberg@lumc.nl.; Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands. M.Roestenberg@lumc.nl., Janse CJ; Malaria Research Group, Department of Parasitology, Leiden University medical Center, Leiden, The Netherlands. c.j.janse@lumc.nl.
Jazyk: angličtina
Zdroj: NPJ vaccines [NPJ Vaccines] 2022 Nov 04; Vol. 7 (1), pp. 139. Date of Electronic Publication: 2022 Nov 04.
DOI: 10.1038/s41541-022-00558-x
Abstrakt: 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.
(© 2022. The Author(s).)
Databáze: MEDLINE
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