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Protective efficacy and safety of liver stage attenuated malaria parasites

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 subsequ...

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Autores principales: Kumar, Hirdesh, Sattler, Julia Magdalena, Singer, Mirko, Heiss, Kirsten, Reinig, Miriam, Hammerschmidt-Kamper, Christiane, Heussler, Volker, Mueller, Ann-Kristin, Frischknecht, Friedrich
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4886212/
https://www.ncbi.nlm.nih.gov/pubmed/27241521
http://dx.doi.org/10.1038/srep26824
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author Kumar, Hirdesh
Sattler, Julia Magdalena
Singer, Mirko
Heiss, Kirsten
Reinig, Miriam
Hammerschmidt-Kamper, Christiane
Heussler, Volker
Mueller, Ann-Kristin
Frischknecht, Friedrich
author_facet Kumar, Hirdesh
Sattler, Julia Magdalena
Singer, Mirko
Heiss, Kirsten
Reinig, Miriam
Hammerschmidt-Kamper, Christiane
Heussler, Volker
Mueller, Ann-Kristin
Frischknecht, Friedrich
author_sort Kumar, Hirdesh
collection PubMed
description 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.
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spelling pubmed-48862122016-06-08 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 Sci Rep Article 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. Nature Publishing Group 2016-05-31 /pmc/articles/PMC4886212/ /pubmed/27241521 http://dx.doi.org/10.1038/srep26824 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Kumar, Hirdesh
Sattler, Julia Magdalena
Singer, Mirko
Heiss, Kirsten
Reinig, Miriam
Hammerschmidt-Kamper, Christiane
Heussler, Volker
Mueller, Ann-Kristin
Frischknecht, Friedrich
Protective efficacy and safety of liver stage attenuated malaria parasites
title Protective efficacy and safety of liver stage attenuated malaria parasites
title_full Protective efficacy and safety of liver stage attenuated malaria parasites
title_fullStr Protective efficacy and safety of liver stage attenuated malaria parasites
title_full_unstemmed Protective efficacy and safety of liver stage attenuated malaria parasites
title_short Protective efficacy and safety of liver stage attenuated malaria parasites
title_sort protective efficacy and safety of liver stage attenuated malaria parasites
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4886212/
https://www.ncbi.nlm.nih.gov/pubmed/27241521
http://dx.doi.org/10.1038/srep26824
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