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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; Murphy, Sean C; Foquet, Lander; Moita, Diana; Mendes, António M; Prudêncio, Miguel; Dechering, Koen J; Heussler, Volker T; Pain, Arnab; Wilder, Brandon K; Roestenberg, Meta; Janse, Chris J.
Afiliación
  • 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.
  • Othman AS; Department of Cellular Architecture Studies, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan.
  • Kolli SK; Universiti Sultan Zainal Abidin, Faculty of Health Sciences, Terengganu, Malaysia.
  • Lamers OAC; Malaria Research Group, Department of Parasitology, Leiden University medical Center, Leiden, The Netherlands.
  • Roques M; Center for Global Health and Infectious Diseases Research, College of Public Health, University of South Florida, Tampa, FL, USA.
  • Stanway RR; Malaria Research Group, Department of Parasitology, Leiden University medical Center, Leiden, The Netherlands.
  • Murphy SC; Institute of Cell Biology, University of Bern, Bern, Switzerland.
  • Foquet L; Institute of Cell Biology, University of Bern, Bern, Switzerland.
  • Moita D; Multidisciplinary Center for Infectious Diseases (MCID), University of Bern, Bern, Switzerland.
  • Mendes AM; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA.
  • Prudêncio M; Yecuris Corporation, Tualatin, OR, USA.
  • Dechering KJ; Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.
  • Heussler VT; Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.
  • Pain A; Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.
  • Wilder BK; TropIQ Health Sciences, Nijmegen, the Netherlands.
  • Roestenberg M; Institute of Cell Biology, University of Bern, Bern, Switzerland.
  • Janse CJ; Pathogen Genomics Laboratory, Biological and Environmental Sciences and Engineering (BESE) Division, King Abdullah University of Science and Technology (KAUST), Thuwal, Kingdom of Saudi Arabia.
NPJ Vaccines ; 7(1): 139, 2022 Nov 04.
Article en En | MEDLINE | ID: mdl-36333336
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: NPJ Vaccines Año: 2022 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: NPJ Vaccines Año: 2022 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Reino Unido