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

van Dijk, Melissa R; Douradinha, Bruno; Franke-Fayard, Blandine; Heussler, Volker; van Dooren, Maaike W; van Schaijk, Ben; van Gemert, Geert-Jan; Sauerwein, Robert W; Mota, Maria M; Waters, Andrew P; Janse, Chris J (2005). Genetically attenuated, P36p-deficient malarial sporozoites induce protective immunity and apoptosis of infected liver cells. Proceedings of the National Academy of Sciences of the United States of America - PNAS, 102(34), pp. 12194-12199. National Academy of Sciences NAS 10.1073/pnas.0500925102

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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.

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:

0027-8424

Publisher:

National Academy of Sciences NAS

Language:

English

Submitter:

Volker Heussler

Date Deposited:

06 Jul 2016 11:28

Last Modified:

07 Jul 2016 04:35

Publisher DOI:

10.1073/pnas.0500925102

PubMed ID:

16103357

BORIS DOI:

10.7892/boris.84074

URI:

https://boris.unibe.ch/id/eprint/84074

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