Modifying the cellular transport of DNA-based vaccines alters the immune response to hantavirus nucleocapsid protein.
Puumala virus is a member of the hantavirus genus (family Bunyaviridae) and is one of the causative agents of hemorrhagic fever with renal syndrome (HFRS) in Europe. A genetic vaccination approach was conducted to investigate if the immune response could be modulated using different cellular secretion and/or localisation signals, and the immune responses were analysed in BALB/c mice and in a bank vole infectious model. Rodents vaccinated with DNA constructs encoding the antigen fused to an amino-terminal secretion signal raised significantly higher antibody levels when compared to using constructs lacking secretion signals. Furthermore, the ratios of the IgG subclasses (IgG2a/IgG1) were raised by the use of cellular localisation signals, indicating a more pronounced Th1-type of immune response. The majority of the mice, or bank voles, immunised with DNA encoding a secreted form of the antigen showed a positive lymphoproliferative response and were protected against challenge with Puumala virus (strain Kazan-wt).
Bucht
G
G
Department of Medical Countermeasures, Division of NBC Defence, Swedish Defence Research Agency, SE-901 82, Umeå, Sweden. goran.bucht@foi.se
Sjölander
K B
KB
Eriksson
S
S
Lindgren
L
L
Lundkvist A
Elgh
F
F
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D003411:Arvicolinae; D001483:Base Sequence; D001693:Biological Transport, Active; D019556:COS Cells; D017931:DNA Primers / Q000235:genetics; D006476:Orthohantavirus / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D007114:Immunization; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D019251:Nucleocapsid / Q000235:genetics* / Q000276:immunology*; D019590:Nucleocapsid Proteins; D021382:Protein Sorting Signals / Q000235:genetics; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology / Q000493:pharmacokinetics*; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology / Q000493:pharmacokinetics*
D000914:Antibodies, Viral; D017931:DNA Primers; D019590:Nucleocapsid Proteins; D021382:Protein Sorting Signals; D019444:Vaccines, DNA; D014765:Viral Vaccines; C100886:nucleocapsid protein, Puumala virus