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Infection and Immunity, May 2005, p. 2974-2985, Vol. 73, No. 5
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.5.2974-2985.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Induction of Strain-Transcending Immunity against Plasmodium chabaudi adami Malaria with a Multiepitope DNA Vaccine

T. Scorza,1,2 K. Grubb,3 P. Smooker,4 A. Rainczuk,3 D. Proll,5,6 and T. W. Spithill2,3*

Departement de Sciences Biologiques, Université du Québec à Montréal, 1200 Rue Saint Alexandre, S-2055, Montréal, Québec H3B 3H5, Canada,1 Centre for Host-Parasite Interactions,2 Institute of Parasitology, McGill University, 21111 Lakeshore Road, Ste.-Anne-de-Bellevue, H9X3V9, Quebec, Canada,3 Department of Biotechnology and Environmental Biology, RMIT University, P.O. Box 71, 3083, Bundoora, Victoria, Australia,4 Department of Biochemistry & Molecular Biology, P.O. Box 13D, Monash University, Victoria 3800, Australia,5 Eijkman Institute for Molecular Biology, Jakarta Pusat 10430, Indonesia6

Received 11 October 2004/ Returned for modification 22 November 2004/ Accepted 21 January 2005

A major goal of current malaria vaccine programs is to develop multivalent vaccines that will protect humans against the many heterologous malaria strains that circulate in endemic areas. We describe a multiepitope DNA vaccine, derived from a genomic Plasmodium chabaudi adami DS DNA expression library of 30,000 plasmids, which induces strain-transcending immunity in mice against challenge with P. c. adami DK. Segregation of this library and DNA sequence analysis identified vaccine subpools encoding open reading frames (ORFs)/peptides of >9 amino acids [aa] (the V9+ pool, 303 plasmids) and >50 aa (V50+ pool, 56 plasmids), respectively. The V9+ and V50+ plasmid vaccine subpools significantly cross-protected mice against heterologous P. c. adami DK challenge, and protection correlated with the induction of both specific gamma interferon production by splenic cells and opsonizing antibodies. Bioinformatic analysis showed that 22 of the V50+ ORFs were polypeptides conserved among three or more Plasmodium spp., 13 of which are predicted hypothetical proteins. Twenty-nine of these ORFs are orthologues of predicted Plasmodium falciparum sequences known to be expressed in the blood stage, suggesting that this vaccine pool encodes multiple blood-stage antigens. The results have implications for malaria vaccine design by providing proof-of-principle that significant strain-transcending immunity can be induced using multiepitope blood-stage DNA vaccines and suggest that both cellular responses and opsonizing antibodies are necessary for optimal protection against P. c. adami.

* Corresponding author. Mailing address: Institute of Parasitology, McGill University, 21111 Lakeshore Road, Ste.-Anne-De-Bellevue, Quebec, Canada H9X3V9. Phone: 1-514-398 8668. Fax: 1-514-398 7857. E-mail: terry.spithill{at}mcgill.ca.

Editor: W. A. Petri, Jr.

Infection and Immunity, May 2005, p. 2974-2985, Vol. 73, No. 5
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.5.2974-2985.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.





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