TITLE

Genetically Attenuated Plasmodium berghei Liver Stages Induce Sterile Protracted Protection That Is Mediated by Major Histocompatibility Complex Class I-Dependent Interferon–γ–Producing CD8+ T Cells

AUTHOR(S)
Jobe, Ousman; Lumsden, Joanne; Mueller, Ann-Kristin; Williams, Jackie; Silva-Rivera, Hilda; Kappe, Stefan H. I.; Schwenk, Robert J.; Matuschewski, Kai; Krzych, Urszula
PUB. DATE
August 2007
SOURCE
Journal of Infectious Diseases;8/15/2007, Vol. 196 Issue 4, p599
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
At present, radiation-attenuated plasmodia sporozoites (γ-spz) is the only vaccine that induces sterile and lasting protection in malaria-naive humans and laboratory rodents. However, γ-spz are not without risks. For example, the heterogeneity of the γ-spz could explain occasional breakthrough infections. To avoid this possibility, we constructed a double-knockout P. berghei parasite by removing 2 genes, UIS3 and UIS4, that are up-regulated in infective spz.We evaluated the double-knockout Pbuis3(—)/4(—) parasites for protective efficacy and the contribution of CD8+ T cells to protection. Pbuis3(—)/4(—) spz induced sterile and protracted protection in C57BL/6 mice. Protection was linked to CD8+ T cells, given that mice deficient in β2m were not protected. Pbuis3(—)/4(—) spz-immune CD8+ T cells consisted of effector/memory phenotypes and produced interferon-γ. On the basis of these observations, we propose that the development of genetically attenuated P. falciparum parasites is warranted for tests in clinical trials as a pre-erythrocytic stage vaccine candidate.
ACCESSION #
26449991

 

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