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Infection and Immunity, January 2004, p. 253-259, Vol. 72, No. 1
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.1.253-259.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Induction of Plasmodium falciparum Transmission-Blocking Antibodies in Nonhuman Primates by a Combination of DNA and Protein Immunizations

Cevayir Coban,1 Mario T. Philipp,2 Jeanette E. Purcell,3 David B. Keister,4 Mobolaji Okulate,1 Dale S. Martin,2 and Nirbhay Kumar1*

Department of Molecular Microbiology and Immunology, Johns Hopkins Malaria Research Institute, The Johns Hopkins University Bloomberg School of Public Health, Baltimore,1 Malaria Vaccines Development Unit, National Institutes of Health, Bethesda, Maryland,4 Divisions of Bacteriology and Parasitology,2 Veterinary Medicine, Tulane National Primate Research Center, Tulane University Health Sciences Center, Covington, Louisiana3

Received 14 August 2003/ Returned for modification 29 September 2003/ Accepted 14 October 2003

Malaria transmission-blocking vaccination can effectively reduce and/or eliminate transmission of parasites from the human host to the mosquito vector. The immunity achieved by inducing an antibody response to surface antigens of male and female gametes and parasite stages in the mosquito. Our laboratory has developed DNA vaccine constructs, based on Pfs25 (a Plasmodium falciparum surface protein of 25 kDa), that induce a transmission-blocking immune response in mice (C. A. Lobo, R. Dhar, and N. Kumar, Infect. Immun. 67:1688-1693, 1999). To evaluate the safety, immunogenicity, and efficacy of the Pfs25 DNA vaccine in nonhuman primates, we immunized rhesus macaques (Macaca mulatta) with a DNA vaccine plasmid encoding Pfs25 or a Pfg27-Pfs25 hybrid or with the plasmid (empty plasmid) alone. Immunization with four doses of these DNA vaccine constructs elicited antibody titers that were high but nonetheless unable to reduce the parasite's infectivity in membrane feeding assays. Further boosting of the antibody response with recombinant Pfs25 formulated in Montanide ISA-720 increased antibody titers (30-fold) and significantly blocked transmission of P. falciparum gametocytes to Anopheles mosquitoes (~90% reduction in oocyst numbers in the midgut). Our data show that a DNA prime-protein boost regimen holds promise for achieving transmission-blocking immunity in areas where malaria is endemic and could be effective in eradicating malaria in isolated areas where the level of malaria endemicity is low.

* Corresponding author. Mailing address: Department of Molecular Microbiology and Immunology, Johns Hopkins Malaria Research Institute, The Johns Hopkins University Bloomberg School of Public Health, 615 N. Wolfe St., Baltimore, MD 21205. Phone: (410) 955-7177. Fax: (410) 955-0105. E-mail: nkumar{at}jhsph.edu.

Editor: W. A. Petri, Jr.

Infection and Immunity, January 2004, p. 253-259, Vol. 72, No. 1
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.1.253-259.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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