Dissection-independent production of Plasmodium sporozoites from whole mosquitoes

Joshua Blight, Katarzyna A. Sala, Erwan Atcheson, Holger Kramer, Aadil El Turabi, Eliana Real, Farah A. Dahalan, Paulo Bettencourt, Emma Dickinson-Craig, Eduardo Alves, Ahmed M. Salman, Chris J. Janse, Frances M. Ashcroft, Adrian Vs Hill, Arturo Reyes-Sandoval, Andrew M. Blagborough, Jake Baum*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Progress towards a protective vaccine against malaria remains slow. To date, only limited protection has been routinely achieved following immunisation with either whole-parasite (sporozoite) or subunit-based vaccines. One major roadblock to vaccine progress, and to pre-erythrocytic parasite biology in general, is the continued reliance on manual salivary gland dissection for sporozoite isolation from infected mosquitoes. Here, we report development of a multi-step method, based on batch processing of homogenised whole mosquitoes, slurry, and density-gradient filtration, which combined with free-flow electrophoresis rapidly produces a pure, infective sporozoite inoculum. Human-infective Plasmodium falciparum and rodent-infective Plasmodium berghei sporozoites produced in this way are two-To threefold more infective than salivary gland dissection sporozoites in in vitro hepatocyte infection assays. In an in vivo rodent malaria model, the same P. berghei sporozoites confer sterile protection from mosquito-bite challenge when immunisation is delivered intravenously or 60 70% protection when delivered intramuscularly. By improving purity, infectivity, and immunogenicity, this method represents a key advancement in capacity to produce researchgrade sporozoites, which should impact delivery of a wholeparasite based malaria vaccine at scale in the future.
Original languageEnglish
Article numbere202101094
JournalLife Science Alliance
Volume4
Issue number7
DOIs
Publication statusPublished - Jul 2021
Externally publishedYes

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