Protective efficacy and safety of liver stage attenuated malaria parasites

Kumar, Hirdesh; Sattler, Julia Magdalena; Singer, Mirko; Heiss, Kirsten; Reinig, Miriam; Hammerschmidt-Kamper, Christiane; Heussler, Volker; Mueller, Ann-Kristin; Frischknecht, Friedrich (2016). Protective efficacy and safety of liver stage attenuated malaria parasites. Scientific Reports, 6, p. 26824. Nature Publishing Group 10.1038/srep26824

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During the clinically silent liver stage of a Plasmodium infection the parasite replicates from a single sporozoite into thousands of merozoites. Infection of humans and rodents with large numbers of sporozoites that arrest their development within the liver can cause sterile protection from subsequent infections. Disruption of genes essential for liver stage development of rodent malaria parasites has yielded a number of attenuated parasite strains. A key question to this end is how increased attenuation relates to vaccine efficacy. Here, we generated rodent malaria parasite lines that arrest during liver stage development and probed the impact of multiple gene deletions on attenuation and protective efficacy. In contrast to P. berghei strain ANKA LISP2(-) or uis3(-) single knockout parasites, which occasionally caused breakthrough infections, the double mutant lacking both genes was completely attenuated even when high numbers of sporozoites were administered. However, different vaccination protocols showed that LISP2(-) parasites protected better than uis3(-) and double mutants. Hence, deletion of several genes can yield increased safety but might come at the cost of protective efficacy.

Item Type:

Journal Article (Original Article)

Division/Institute:

08 Faculty of Science > Department of Biology > Institute of Cell Biology > Malaria
08 Faculty of Science > Department of Biology > Institute of Cell Biology

UniBE Contributor:

Heussler, Volker

Subjects:

500 Science > 570 Life sciences; biology

ISSN:

2045-2322

Publisher:

Nature Publishing Group

Language:

English

Submitter:

Volker Heussler

Date Deposited:

01 Jun 2016 14:39

Last Modified:

01 Jun 2016 14:39

Publisher DOI:

10.1038/srep26824

PubMed ID:

27241521

URI:

https://boris.unibe.ch/id/eprint/83474

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