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Infection and Immunity, January 2004, p. 584-588, Vol. 72, No. 1
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.1.584-588.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Effect of CpG Oligodeoxynucleotides on the Immunogenicity of Pfs25, a Plasmodium falciparum Transmission-Blocking Vaccine Antigen

Cevayir Coban,1 Ken J. Ishii,2 Anthony W. Stowers,3,{dagger} David B. Keister,3 Dennis M. Klinman,2 and Nirbhay Kumar1*

Department of Molecular Microbiology and Immunology, Malaria Research Institute, Bloomberg School of Public Health, Johns Hopkins University, Baltimore,1 Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda,2 Malaria Vaccine Development Unit, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland3

Received 14 August 2003/ Returned for modification 3 September 2003/ Accepted 29 September 2003

Antibodies directed against Pfs25, a protein present on the surface of zygotes and ookinetes of Plasmodium falciparum, completely block pathogen transmission. We evaluated the immunomodulatory effect of CpG oligodeoxynucleotides (ODN) on the immunogenicity of recombinant Pfs25 (rPfs25) formulated in alum (Al). Immunization of mice with rPfs25 plus CpG ODN improved both the antibody titer (a 30-fold-higher antibody response than that with rPfs25-Al alone) and avidity. Coadministration of CpG ODN dramatically enhanced the titer of immunoglobulin G2A (IgG2a) compared to the titer of the IgG1-dominant response caused by rPfs25-Al alone, and the sera from the CpG ODN-coadministered group completely blocked the transmission of P. falciparum parasites to mosquitoes, as determined by membrane feeding assays. However, transmission-blocking experiments revealed that blocking efficacy was dependent on high-titer antibody levels, independent of isotypes. These results suggest that CpG ODN can be used as an adjuvant to enhance the immunogenicity of rPfs25 as a malaria transmission-blocking vaccine.

* Corresponding author. Mailing address: Department of Molecular Microbiology and Immunology, Johns Hopkins 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.

{dagger} Present address: CSL Ltd., Parkville, Victoria 3052, Australia.

Infection and Immunity, January 2004, p. 584-588, Vol. 72, No. 1
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.1.584-588.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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