Gene gun bombardment with gold particles displays a particular Th2-promoting signal that over-rules the Th1-inducing effect of immunostimulatory CpG motifs in DNA vaccines.
The mode of administering a DNA vaccine can influence the type of immune response induced by the vaccine. For instance, application of a DNA vaccine by gene gun typically induces a Th2-type reaction, whereas needle inoculation triggers a Th1 response. It has been proposed that the approximately 100-fold difference in the amount of DNA administered by these two methods is the critical factor determining whether a Th1 or a Th2 response is made. To test this hypothesis, BALB/c mice were immunized with two plasmid DNA constructs encoding different proteins (OspC/ZS7 of Borrelia burgdorferi and Bet v 1a, the major birch pollen allergen). Both vaccines were applied by needle and/or by gene gun immunization at the same and at different sites of injection. An analysis of the IgG subclass distribution and measurement of IFN-gamma after antigen-specific lymphoproliferation does not support the widely accepted view that Th2-type immunity induced by gene gun application is solely due to the low amount of injected plasmid DNA thus falling below the critical concentration of CpG motifs necessary for Th1-induction. Furthermore, the data also indicate a strong and even systemic adjuvant effect of the gene gun shot itself.
Weiss
Richard
R
Institute of Chemistry and Biochemistry, University of Salzburg, Hellbrunner Street 34, A-5020 Salzburg, Austria.
Scheiblhofer
Sandra
S
Freund
Johann
J
Ferreira
Fatima
F
Livey
Ian
I
Thalhamer
Josef
J
D000276:Adjuvants, Immunologic; D000485:Allergens / Q000235:genetics / Q000276:immunology; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology; D052179:Antigens, Plant; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000276:immunology; D029662:Betula / Q000235:genetics / Q000276:immunology; D019470:Biolistics; D025065:Borrelia burgdorferi / Q000235:genetics / Q000276:immunology; D018899:CpG Islands / Q000276:immunology*; D004274:DNA, Recombinant / Q000008:administration & dosage / Q000235:genetics; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D005822:Genetic Vectors / Q000008:administration & dosage* / Q000235:genetics; D006046:Gold; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology; D007271:Injections, Intradermal; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009339:Needles; D010940:Plant Proteins / Q000235:genetics / Q000276:immunology; D011058:Pollen; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D014611:Vaccination / Q000295:instrumentation / Q000379:methods*; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000276:immunology
D000276:Adjuvants, Immunologic; D000485:Allergens; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D052179:Antigens, Plant; D001425:Bacterial Outer Membrane Proteins; D004274:DNA, Recombinant; D007074:Immunoglobulin G; C079616:OspC protein; D010940:Plant Proteins; D019444:Vaccines, DNA; C061312:Bet v 1 allergen, Betula; D015847:Interleukin-4; D006046:Gold; D007371:Interferon-gamma