A glycosylphosphatidylinositol anchor signal sequence enhances the immunogenicity of a DNA vaccine encoding Plasmodium falciparum sexual-stage antigen, Pfs230.
Mammalian expression vectors encoding region C of malaria transmission-blocking vaccine candidate Pfs230 (aa 443-1132) with and without a 3' glycosylphosphatidylinositol (GPI) anchor signal sequence were tested for their immunogenicity in mice. The plasmid containing the GPI anchor signal sequence consistently induced higher titers of anti-Pfs230 antibodies using three delivery systems: intramuscular (i.m.), intradermal (i.d.), and gene gun (g.g.). In contrast, the isotype profile elicited varied depending on the delivery system and was not effected by the presence of the GPI anchor sequence. Both gene gun and intradermal administration induced primarily an IgG1 response, while intramuscular injection induced both IgG1 and IgG2a antibodies. Regardless of the mode of delivery, all the plasmids encoding Pfs230 region C primed for a mixed IgG1/IgG2a response to an intraperitoneal (i.p.) injection of E. coli-produced recombinant Pfs230 region C. None of these vaccination strategies were more effective than r230/MBP.C alone in generating malaria transmission-blocking immunity.
Fanning
Sarah L
SL
Department of Biology, Loyola University Chicago, 6525 North Sheridan Road, Chicago, IL, 60626, USA.
Czesny
Beata
B
Sedegah
Martha
M
Carucci
Daniel J
DJ
van Gemert
Geert Jan
GJ
Eling
Wijnand
W
Williamson
Kim C
KC
D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics* / Q000276:immunology*; D019556:COS Cells; D004279:DNA, Viral / Q000235:genetics / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D017261:Glycosylphosphatidylinositols / Q000737:chemistry*; D015151:Immunoblotting; D017780:Malaria Vaccines / Q000276:immunology*; D016778:Malaria, Falciparum / Q000276:immunology* / Q000635:transmission; D051379:Mice; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence; D010963:Plasmodium falciparum / Q000235:genetics* / Q000276:immunology*; D010959:Tissue Plasminogen Activator / Q000276:immunology; D014162:Transfection; D019444:Vaccines, DNA / Q000276:immunology*
D000953:Antigens, Protozoan; D004279:DNA, Viral; D017261:Glycosylphosphatidylinositols; D017780:Malaria Vaccines; D019444:Vaccines, DNA; D010959:Tissue Plasminogen Activator