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Infection and Immunity, October 2004, p. 5565-5573, Vol. 72, No. 10
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.10.5565-5573.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

A Bicistronic DNA Vaccine Containing Apical Membrane Antigen 1 and Merozoite Surface Protein 4/5 Can Prime Humoral and Cellular Immune Responses and Partially Protect Mice against Virulent Plasmodium chabaudi adami DS Malaria

A. Rainczuk,1,2 T. Scorza,3 T. W. Spithill,3,4* and P. M. Smooker5

Department of Biochemistry and Molecular Biology, Monash University, Clayton,1 Department of Biotechnology and Environmental Biology, RMIT University, Bundoora, Victoria,5 The Cooperative Research Centre for Vaccine Technology, The Bancroft Centre, Royal Brisbane Hospital, Brisbane, Queensland Australia,2 Institute of Parasitology,3 FQRNT Centre for Host-Parasite Interactions McGill University, Ste. Anne de Bellevue, Quebec, Canada4

Received 24 February 2004/ Returned for modification 4 April 2004/ Accepted 24 June 2004

The ultimate malaria vaccine will require the delivery of multiple antigens from different stages of the complex malaria life cycle. In order to efficiently deliver multiple antigens with use of DNA vaccine technology, new antigen delivery systems must be assessed. This study utilized a bicistronic vector construct, containing an internal ribosome entry site, expressing a combination of malarial candidate antigens: merozoite surface protein 4/5 (MSP4/5) (fused to a monocyte chemotactic protein 3 chemoattractant sequence) and apical membrane antigen 1 (AMA-1) (fused to a tissue plasminogen activator secretion signal). Transfection of COS 7 cells with bicistronic plasmids resulted in production and secretion of both AMA-1 and MSP4/5 in vitro. Vaccination of BALB/c mice via intraepidermal gene gun and intramuscular routes against AMA-1 and MSP4/5 resulted in antibody production and significant in vitro proliferation of splenocytes stimulated by both AMA-1 and MSP4/5. Survival of BALB/c mice vaccinated with bicistronic constructs after lethal Plasmodium chabaudi adami DS erythrocytic-stage challenge was variable, although significant increases in survival and reductions in peak parasitemia were observed in several challenge trials when the vaccine was delivered by the intramuscular route. This study using a murine model demonstrates that the delivery of malarial antigens via bicistronic vectors is feasible. Further experimentation with bicistronic delivery systems is required for the optimization and refinement of DNA vaccines to effectively prime protective immune responses against malaria.

* Corresponding author. Mailing address: Institute of Parasitology, McGill University, 21111 Lakeshore Rd., Ste. Anne de Bellevue, Quebec, Canada H9X 3V9. Phone: (514) 398-8668. Fax: (514) 398-7857. E-mail: terry.spithill{at}mcgill.ca.

Editor: W. A. Petri, Jr.

Infection and Immunity, October 2004, p. 5565-5573, Vol. 72, No. 10
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.10.5565-5573.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.





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