title: Enhancement of DNA vaccine potency by linkage of Plasmodium falciparum malarial antigen gene fused with a fragment of HSP70 gene.
abstract: Finding an appropriate adjuvant for human vaccination is crucial. HSPs have been shown to act as adjuvants when coadministered with peptide antigens or given as fusion proteins. However, there is a potential risk of autoimmunity when using the complete molecules because HSPs are evolutionary conserved. To overcome this, we first evaluated the adjuvant effect of a less conserved fragment of Plasmodium falciparum HSP70 (Pf70C) as compared it to that of the whole HSP70 molecule from Trypanosoma cruzi (TcHSP70). We found that Pf70C exhibited similar adjuvant properties as the whole molecule. We then evaluated the adjuvant potential of Pf70C for the malarial antigen EB200 in a chimeric DNA construct. No appreciable levels of EB200 specific antibodies were detected in mice immunized with the DNA constructs only. However, the DNA immunization efficiently primed the immune system, as indicated by the strong Th-1 antibody response elicited by a subsequent boosting with the corresponding recombinant fusion proteins. In contrast, while no such priming effect was observed for ex vivo IFN-gamma production, stimulation with the HSP chimeric fusion protein induced an enhanced secretion of IFN-gamma in vitro as compared to other proteins used. Our results emphasize the potential of HSPs as adjuvants in subunit vaccines.
authors.affiliation: Department of Immunology, Wenner-Gren Institute, Stockholm University, SE-10691 Stockholm, Sweden.
authors.forename: Khaleda Rahman
authors.initials: KR
authors.lastname: Qazi
authors.forename: Maria
authors.initials: M
authors.lastname: Wikman
authors.forename: Nina-Maria
authors.initials: NM
authors.lastname: Vasconcelos
authors.forename: Klavs
authors.initials: K
authors.lastname: Berzins
authors.forename: Stefan
authors.initials: S
authors.lastname: Ståhl
authors.forename: Carmen
authors.initials: C
authors.lastname: Fernández
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000953:Antigens, Protozoan / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology*; D019556:COS Cells; D002522:Chlorocebus aethiops; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D006801:Humans; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology*; D016778:Malaria, Falciparum / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008969:Molecular Sequence Data; D014349:Trypanosoma cruzi / Q000235:genetics / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
chemical_list: D000953:Antigens, Protozoan; D018840:HSP70 Heat-Shock Proteins; D017780:Malaria Vaccines; D019444:Vaccines, DNA