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Infection and Immunity, May 2005, p. 2863-2872, Vol. 73, No. 5
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.5.2863-2872.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Boosting of DNA Vaccine-Elicited Gamma Interferon Responses in Humans by Exposure to Malaria Parasites

Ruobing Wang,^1,2, Thomas L. Richie,¹ Maria Fe Baraceros,^1,2 Nancy Rahardjo,^1,2 Tanya Gay,^1,2 Jo-Glenna Banania,^1,2 Yupin Charoenvit,¹ Judith E. Epstein,¹ Thomas Luke,^1,3 Daniel A. Freilich,¹ Jon Norman,⁴ and Stephen L. Hoffman^1*

Malaria Program, Naval Medical Research Center, Silver Spring, Maryland 20910,¹ Henry M. Jackson Foundation, Rockville, Maryland 20852,² Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814,³ Vical Incorporated, San Diego, California 92121⁴

Received 23 August 2004/ Returned for modification 13 October 2004/ Accepted 11 December 2004

A mixture of DNA plasmids expressing five Plasmodium falciparum pre-erythrocyte-stage antigens was administered with or without a DNA plasmid encoding human granulocyte-macrophage colony-stimulating factor (hGM-CSF) as an immune enhancer. After DNA immunization, antigen-specific gamma interferon (IFN-) responses were detected by ELISPOT in 15/31 volunteers to multiple class I- and/or class II-restricted T-cell epitopes derived from all five antigens. Responses to multiple epitopes (7) were detected simultaneously in some volunteers. By 4 weeks after challenge with P. falciparum parasites, 23/31 volunteers had positive IFN- responses and the magnitude of responses was increased from 2- to 143-fold. Nonetheless, none was protected against malaria. Volunteers who received hGM-CSF had a reduced frequency of IFN- responses to class I peptides compared to those who only received plasmids expressing P. falciparum proteins before challenge (3/23 versus 3/8; P = 0.15) or after parasite challenge (4/23 versus 5/8; P = 0.015) but not to class II peptides before or after challenge. The responses to one antigen (P. falciparum circumsporozoite protein [PfCSP]) were similar among volunteers who received the five-gene mixture compared to volunteers who only received the PfCSP DNA plasmid in a previous study. In summary, DNA-primed IFN- responses were boosted in humans by exposure to native antigen on parasites, coadministration of a plasmid expressing hGM-CSF had a negative effect on boosting of class I-restricted IFN- responses, and there was no evidence that immunization with PfCSP DNA in the mixture reduced T-cell responses to PfCSP compared to when it was administered alone.

Editor: W. A. Petri, Jr.

Present address: The Institute for Genomic Research, Rockville, MD 20850.

Present address: Digene Corporation, Gaithersburg, MD 20878.

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