Genetically attenuated, P36p-deficient malarial sporozoites induce protective immunity and apoptosis of infected liver cells.

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Publication year
2005Source
Proceedings of the National Academy of Sciences USA, 102, 34, (2005), pp. 12194-12199ISSN
Publication type
Article / Letter to editor

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Organization
Medical Microbiology
Former Organization
Radboud University Nijmegen Medical Centre
Journal title
Proceedings of the National Academy of Sciences USA
Volume
vol. 102
Issue
iss. 34
Page start
p. 12194
Page end
p. 12199
Subject
N4i 3: Poverty-related infectious diseases; N4i 4: Auto-immunity, transplantation and immunotherapy; NCMLS 1: Infection and autoimmunity; UMCN 4.1: Microbial pathogenesis and host defenseAbstract
Immunization with Plasmodium sporozoites that have been attenuated by gamma-irradiation or specific genetic modification can induce protective immunity against subsequent malaria infection. The mechanism of protection is only known for radiation-attenuated sporozoites, involving cell-mediated and humoral immune responses invoked by infected hepatocytes cells that contain long-lived, partially developed parasites. Here we analyzed sporozoites of Plasmodium berghei that are deficient in P36p (p36p(-)), a member of the P48/45 family of surface proteins. P36p plays no role in the ability of sporozoites to infect and traverse hepatocytes, but p36p(-) sporozoites abort during development within the hepatocyte. Immunization with p36p(-) sporozoites results in a protective immunity against subsequent challenge with infectious wild-type sporozoites, another example of a specifically genetically attenuated sporozoite (GAS) conferring protective immunity. Comparison of biological characteristics of p36p(-) sporozoites with radiation-attenuated sporozoites demonstrates that liver cells infected with p36p(-) sporozoites disappear rapidly as a result of apoptosis of host cells that may potentiate the immune response. Such knowledge of the biological characteristics of GAS and their evoked immune responses are essential for further investigation of the utility of an optimized GAS-based malaria vaccine.
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- Faculty of Medical Sciences [81054]
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