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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,{dagger} 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. Hoffman1*

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-{gamma}) 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-{gamma} 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-{gamma} 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-{gamma} 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-{gamma} 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.

* Corresponding author. Present address: Sanaria, Inc., 12115 Parklawn Drive, Suite L, Rockville, MD 20852. Phone: (301) 770-3222. Fax: (301) 770-5554. E-mail: slhoffman{at}sanaria.com.

Editor: W. A. Petri, Jr.

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

{ddagger} Present address: Digene Corporation, Gaithersburg, MD 20878.

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.



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