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Infection and Immunity, July 2002, p. 3493-3499, Vol. 70, No. 7
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.7.3493-3499.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Persistence of Protective Immunity to Malaria Induced by DNA Priming and Poxvirus Boosting: Characterization of Effector and Memory CD8⁺-T-Cell Populations

Martha Sedegah,^1,2* Gary T. Brice,¹ William O. Rogers,^1, Denise L. Doolan,^1,3 Yupin Charoenvit,¹ Trevor R. Jones,¹ Victoria F. Majam,¹ Arnel Belmonte,¹ Minh Lu,¹ Maria Belmonte,¹ Daniel J. Carucci,¹ and Stephen L. Hoffman^1,

Malaria Program, Naval Medical Research Center, Silver Spring, Maryland 20910-7500,¹ Department of Microbiology, The University of Maryland School of Medicine, Baltimore, Maryland 21201-1559,² Department of Molecular Microbiology and Immunology, School of Hygiene and Public Health, Johns Hopkins University, Baltimore, Maryland 21205-2179³

Received 11 December 2001/ Returned for modification 9 January 2002/ Accepted 10 April 2002

The persistence of immunity to malaria induced in mice by a heterologous DNA priming and poxvirus boosting regimen was characterized. Mice were immunized by priming with DNA vaccine plasmids encoding the Plasmodium yoelii circumsporozoite protein (PyCSP) and murine granulocyte-macrophage colony-stimulating factor and boosting with recombinant vaccinia encoding PyCSP. BALB/c mice immunized with either high-dose (100 µg of p PyCSP plus 30 µg of pGM-CSF) or low-dose (1 µg of p PyCSP plus 1 µg of pGM-CSF DNA) priming were protected against challenge with 50 P. yoelii sporozoites. Protection 2 weeks after immunization was 70 to 100%, persisted at this level for at least 20 weeks, and declined to 30 to 40% by 28 weeks. Eight of eight mice protected at 20 weeks were still protected when rechallenged at 40 weeks. The antigen (Ag)-specific effector CD8⁺-T-cell population present 2 weeks after boosting had ex vivo Ag-specific cytolytic activity, expressed both gamma interferon (IFN-) and tumor necrosis factor alpha, and constituted 12 to 20% of splenic CD8⁺ T cells. In contrast, the memory CD8⁺-Ag-specific-cell population at 28 weeks lacked cytolytic activity and constituted only 6% of splenic CD8⁺ T cells, but at the single-cell level it produced significantly higher levels of IFN- than the effectors. High levels of Ag- or parasite-specific antibodies present 2 weeks after boosting had declined three- to sevenfold by 28 weeks. Low-dose priming was similarly immunogenic and as protective as high-dose priming against a 50-, but not a 250-, sporozoite challenge. These results demonstrate that a heterologous priming and boosting vaccination can provide lasting protection against malaria in this model system.

Editor: W. A. Petri, Jr.

Present address: Naval Medical Research Unit 3, Ghana Detachment, c/o Department of State, Washington, DC 20521-2020.

Present address: Celera Genomics, Rockville, MD 20850.

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