Dissection-independent production of a Plasmodium sporozoites from whole mosquitoes
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Published version
Author(s)
Type
Journal Article
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 research-grade sporozoites, which should impact delivery of a whole-parasite based malaria vaccine at scale in the future.
Date Issued
2021-07-01
Date Acceptance
2021-05-25
Citation
Life Science Alliance, 2021, 4 (7)
ISSN
2575-1077
Publisher
Life Science Alliance
Journal / Book Title
Life Science Alliance
Volume
4
Issue
7
Copyright Statement
© 2021 Blight et al. This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).
License URL
Sponsor
Wellcome Trust
Wellcome Trust
Bill & Melinda Gates Foundation
Grant Number
100993/Z/13/Z
100993/Z/13/Z
OPP1200274
Publication Status
Published
Article Number
ARTN e02101094
Date Publish Online
2021-06-16