Dissection-independent production of a protective whole-sporozoite malaria vaccine
Abstract Complete protection against human malaria challenge has been achieved using infected mosquitoes as the delivery route for immunization withPlasmodiumparasites. Strategies seeking to replicate this efficacy with either a manufactured whole-parasite or subunit vaccine, however, have shown only limited success. A major roadblock to whole parasite vaccine progress and understanding of the human infective sporozoite form in general, is reliance on manual dissection for parasite isolation from infected mosquitoes. We report here the development of a four-step process based on whole mosquito homogenization, slurry and density-gradient filtration, combined with free-flow electrophoresis that is able to rapidly produce a pure, aseptic sporozoite inoculum from hundreds of mosquitoes. MurineP. bergheior human-infectiveP. falciparumsporozoites produced in this way are 2-3-fold more infective within vitrohepatocytes and can confer sterile protection when immunized intravenously with subsequent challenge using a mouse malaria model. Critically, we can also demonstrate for the first time 60-70% protection when the same parasites are administered via intramuscular (i.m.) route. In developing a process amenable to industrialisation and demonstrating efficacy by i.m. route these data represent a major advancement in capacity to produce a whole parasite malaria vaccine at scale.One-Sentence Summary A four-step process for isolating pure infective malaria parasite sporozoites at scale from homogenized whole mosquitoes, independent of manual dissection, is able to produce a whole parasite vaccine inoculum that confers sterilizing protection..
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Preprint| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
bioRxiv.org - (2023) vom: 02. Okt. Zur Gesamtaufnahme - year:2023 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Blight, Joshua [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| Themen: |
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| doi: |
10.1101/2020.06.22.164756 |
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| PPN (Katalog-ID): |
XBI018191266 |
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| 245 | 1 | 0 | |a Dissection-independent production of a protective whole-sporozoite malaria vaccine |
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| 520 | |a Abstract Complete protection against human malaria challenge has been achieved using infected mosquitoes as the delivery route for immunization withPlasmodiumparasites. Strategies seeking to replicate this efficacy with either a manufactured whole-parasite or subunit vaccine, however, have shown only limited success. A major roadblock to whole parasite vaccine progress and understanding of the human infective sporozoite form in general, is reliance on manual dissection for parasite isolation from infected mosquitoes. We report here the development of a four-step process based on whole mosquito homogenization, slurry and density-gradient filtration, combined with free-flow electrophoresis that is able to rapidly produce a pure, aseptic sporozoite inoculum from hundreds of mosquitoes. MurineP. bergheior human-infectiveP. falciparumsporozoites produced in this way are 2-3-fold more infective within vitrohepatocytes and can confer sterile protection when immunized intravenously with subsequent challenge using a mouse malaria model. Critically, we can also demonstrate for the first time 60-70% protection when the same parasites are administered via intramuscular (i.m.) route. In developing a process amenable to industrialisation and demonstrating efficacy by i.m. route these data represent a major advancement in capacity to produce a whole parasite malaria vaccine at scale.One-Sentence Summary A four-step process for isolating pure infective malaria parasite sporozoites at scale from homogenized whole mosquitoes, independent of manual dissection, is able to produce a whole parasite vaccine inoculum that confers sterilizing protection. | ||
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| 700 | 1 | |a Sala, Katarzyna A. |4 aut | |
| 700 | 1 | |a Atcheson, Erwan |4 aut | |
| 700 | 1 | |a Kramer, Holger |4 aut | |
| 700 | 1 | |a El-Turabi, Aadil |0 (orcid)0000-0003-1092-8155 |4 aut | |
| 700 | 1 | |a Real, Eliana |0 (orcid)0000-0002-2502-9374 |4 aut | |
| 700 | 1 | |a Dahalan, Farah A. |0 (orcid)0000-0002-4215-0715 |4 aut | |
| 700 | 1 | |a Bettencourt, Paulo |0 (orcid)0000-0002-4884-5470 |4 aut | |
| 700 | 1 | |a Dickinson, Emma |4 aut | |
| 700 | 1 | |a Alves, Eduardo |4 aut | |
| 700 | 1 | |a Salman, Ahmed M. |0 (orcid)0000-0002-9259-7339 |4 aut | |
| 700 | 1 | |a Janse, Chris J. |0 (orcid)0000-0002-6410-6205 |4 aut | |
| 700 | 1 | |a Ashcroft, Frances |0 (orcid)0000-0002-6970-1767 |4 aut | |
| 700 | 1 | |a Hill, Adrian V. S. |0 (orcid)0000-0003-0900-9629 |4 aut | |
| 700 | 1 | |a Reyes-Sandoval, Arturo |0 (orcid)0000-0002-2648-1696 |4 aut | |
| 700 | 1 | |a Blagborough, Andrew M. |0 (orcid)0000-0002-5257-8475 |4 aut | |
| 700 | 1 | |a Baum, Jake |0 (orcid)0000-0002-0275-352X |4 aut | |
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