title: Cationic influenza virosomes as an adjuvanted delivery system for CTL induction by DNA vaccination.
abstract: DNA vaccines have emerged as an attractive approach to induce CTL responses against cancer and infectious agents in recent years. Although CTL induction by DNA vaccination would be a valuable strategy for controlling viral infections, increasing the potency of DNA vaccines is mandatory before DNA vaccines can make it to the clinic. In this study, we developed and characterized a new and safe adjuvanted delivery system for DNA vaccination using cationic influenza virosomes (CIV). CIV were produced by reconstitution of detergent-solubilized influenza virus membranes in the presence of cationic lipids. Plasmid DNA (pDNA) mixed with these virosomes was efficiently transfected into cells of a mouse macrophage cell line (RAW-Blue cells). Moreover, the cells were effectively activated as demonstrated by production of an NFκB/AP-1-inducible reporter enzyme. Following three intradermal immunizations, CIV-delivered epitope-encoding pDNA induced equal numbers of IFNγ- and granzyme B-producing T cells than a 10-fold higher dose of naked pDNA. Virosomes without cationic lipids also improved induction of cellular immunity by pDNA but to a significantly lower extent than CIV. These findings suggest that pDNA-CIV complexes could be an efficacious delivery system suitable for CTL induction by DNA vaccination.
authors.affiliation: Influenza Research Laboratory, Pasteur Institute of Iran, Tehran, Iran.
authors.forename: Abbas
authors.initials: A
authors.lastname: Jamali
authors.forename: Marijke
authors.initials: M
authors.lastname: Holtrop
authors.forename: Aalzen
authors.initials: A
authors.lastname: de Haan
authors.forename: Hamidreza
authors.initials: H
authors.lastname: Hashemi
authors.forename: Mohammad
authors.initials: M
authors.lastname: Shenagari
authors.forename: Arash
authors.initials: A
authors.lastname: Memarnejadian
authors.forename: Farzin
authors.initials: F
authors.lastname: Roohvand
authors.forename: Farzaneh
authors.initials: F
authors.lastname: Sabahi
authors.forename: Masumeh Tavassoti
authors.initials: MT
authors.lastname: Kheiri
authors.forename: Anke
authors.initials: A
authors.lastname: Huckriede
mesh_terms: D000818:Animals; D002412:Cations / Q000737:chemistry / Q000276:immunology; D002460:Cell Line; D004279:DNA, Viral / Q000235:genetics / Q000276:immunology; D016503:Drug Delivery Systems / Q000379:methods; D004797:Enzyme-Linked Immunosorbent Assay; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D053804:Granzymes / Q000276:immunology / Q000378:metabolism; D007271:Injections, Intradermal; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D008055:Lipids / Q000737:chemistry / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009975:Orthomyxoviridae / Q000276:immunology*; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism; D014162:Transfection; D014611:Vaccination / Q000379:methods*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology; D022701:Virosomes
chemical_list: D002412:Cations; D004279:DNA, Viral; D018984:Epitopes, T-Lymphocyte; D008055:Lipids; D019444:Vaccines, DNA; D014759:Viral Envelope Proteins; D022701:Virosomes; C091015:glycoprotein E2, Hepatitis C virus; D007371:Interferon-gamma; D053804:Granzymes