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* Institut Cochin, Department of Immunology, Université Paris Descartes, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8104,
Institut National de la Santé et de la Recherche Médicale, Unité 567,
Equipe Parasitologie Comparée et Modèles Expérimentaux, Unité Scientifique Muséum 0307, Centre National de la Recherche Scientifique, Institut Fédératif de Recherche 101, Muséum National d’Histoire Naturelle,
Institut National de la Santé et de la Recherche Médicale, Unité 511,
¶ Université Pierre & Marie Curie, Faculté de Médecine Pitié-Salpêtrière,
|| Assistance Publique-Hôpitaux de Paris, Centre Hospitalo-Universitaire Pitié-Salpêtrière, Paris, France;
# Department of Medical Parasitology, New York University School of Medicine, New York, NY 10010;
** Departamento de Parasitologia, Universidade Estadual de Campinas, Campinas-SP, Brazil; and
Singapore Immunology Network, Agency for Science, Technology and Research and, Biopolis, Singapore
Immunity to malaria has long been thought to be stage-specific. In this study we show that immunization of BALB/c mice with live erythrocytes infected with nonlethal strains of Plasmodium yoelii under curative chloroquine cover conferred protection not only against challenge by blood stage parasites but also against sporozoite challenge. This cross-stage protection was dose-dependent and long lasting. CD4+ and CD8+ T cells inhibited malaria liver but not blood stage. Their effect was mediated partially by IFN-
, and was completely dependent of NO. Abs against both pre-erythrocytic and blood parasites were elicited and were essential for protection against blood stage and liver stage parasites. Our results suggest that Ags shared by liver and blood stage parasites can be the foundation for a malaria vaccine that would provide effective protection against both pre-erythrocytic and erythrocytic asexual parasites found in the mammalian host.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by Institut National de la Santé et de la Recherche Médicale. F.T.M.C. was supported by fellowship BEX 0446/98-0 from Coordination for the Improvement of Higher Education Personnel (CAPES) Foundation Brazil. E.B. was supported by a fellowship from Ministère de la Recherche et de la Technologie France. A.M.V. was supported by Fellowship BD/9255/96 from Junta Nacional de Investigação Científica e Tecnológica Portugal. T.V. was supported by Training Grant T32 AI07180 and P.S. by Grant R01 AI056840 from the National Institutes of Health.
2 Address correspondence and reprint request to Dr. Laurent Rénia, Singapore Immunology Network, Agency for Science, Technology and Research, Immunos 3-15, 8A Biomedical Grove, Biopolis, 138648 Singapore. E-mail address: renia_laurent{at}immunol.a-star.edu.sg
3 Abbreviations used in this paper: iRBC, infected RBC; Py-iRBC, P. yoelii 265BY iRBC; Py17X-iRBC, P. yoelii 17X iRBC; SMT, S-methylisothiourea; BKO, B cell-deficient mice.
4 The online version of this article contains supplemental material.
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  A. Trimnell, A. Takagi, M. Gupta, T. L. Richie, S. H. Kappe, and R. Wang Genetically Attenuated Parasite Vaccines Induce Contact-Dependent CD8+ T Cell Killing of Plasmodium yoelii Liver Stage-Infected Hepatocytes J. Immunol., November 1, 2009; 183(9): 5870 - 5878. [Abstract] [Full Text] [PDF]
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