title: Immunomodulation by apoptosis-inducing caspases for an influenza DNA vaccine delivered by gene gun.
abstract: Apoptosis-inducing caspases have been tested for immunomodulatory effect on a gene gun-delivered DNA vaccine which expresses influenza hemagglutinin. Attenuated murine caspase 2 and a chimera of murine caspase 2 prodomain and human caspase 3 strongly enhanced humoral and cell-mediated immune response to hemagglutinin when they were co-administered with an immunogen DNA. In contrast, wild-type caspases did not enhance the DNA-raised immune response. Caspase dose-dependent antibody response curve revealed that the antibody level was in inverse relation to the amount of administered caspase. These findings indicate that bland apoptosis of antigen-harboring cells can elicit enhanced immune responses. Extensive apoptosis interferes with the generation of immune response. Gene gun delivery involving caspases elicited type-2 immune responses that characterized with dominant IL-4 and IgG1 production. ELISPOT assays showed that CD4 T cells were preferentially activated, while CD8 T cell response remained at marginal level. Using attenuated caspases for gene gun DNA vaccination is a useful approach to amplify type-2 immune responses.
authors.affiliation: Division of Microbiology and Immunology, Vaccine Research Center, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Sasaki
authors.forename: K-Q
authors.initials: KQ
authors.lastname: Xin
authors.forename: K
authors.initials: K
authors.lastname: Okudela
authors.forename: K
authors.initials: K
authors.lastname: Okuda
authors.forename: N
authors.initials: N
authors.lastname: Ishii
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D017209:Apoptosis; D019470:Biolistics; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D020169:Caspases / Q000235:genetics*; D006388:Hemagglutinins / Q000235:genetics; D007074:Immunoglobulin G / Q000276:immunology; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D019444:Vaccines, DNA / Q000008:administration & dosage*
chemical_list: D000276:Adjuvants, Immunologic; D006388:Hemagglutinins; D007074:Immunoglobulin G; D007252:Influenza Vaccines; D019444:Vaccines, DNA; D015847:Interleukin-4; D020169:Caspases