title: Effect of CpG oligodeoxynucleotides on the immunogenicity of Pfs25, a Plasmodium falciparum transmission-blocking vaccine antigen.
abstract: 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.
authors.affiliation: Department of Molecular Microbiology and Immunology, Malaria Research Institute, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 21205, USA.
authors.forename: Cevayir
authors.initials: C
authors.lastname: Coban
authors.forename: Ken J
authors.initials: KJ
authors.lastname: Ishii
authors.forename: Anthony W
authors.initials: AW
authors.lastname: Stowers
authors.forename: David B
authors.initials: DB
authors.lastname: Keister
authors.forename: Dennis M
authors.initials: DM
authors.lastname: Klinman
authors.forename: Nirbhay
authors.initials: N
authors.lastname: Kumar
mesh_terms: D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D000915:Antibody Affinity; D007114:Immunization; D007117:Immunization, Secondary; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000276:immunology*; D016778:Malaria, Falciparum / Q000517:prevention & control / Q000635:transmission*; D051379:Mice; D008807:Mice, Inbred BALB C; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage / Q000276:immunology*; D010963:Plasmodium falciparum / Q000276:immunology*; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D000913:Antibodies, Protozoan; C408982:CPG-oligonucleotide; D017780:Malaria Vaccines; D009838:Oligodeoxyribonucleotides; C071284:Pfs25 protein, Plasmodium falciparum; D015800:Protozoan Proteins; C041524:aluminum sulfate