title: Immunization with low doses of HIV-1 tat DNA delivered by novel cationic block copolymers induces CTL responses against Tat.
abstract: Cytotoxic T cell responses are key to the control of intracellular pathogens including HIV-1. In particular, HIV-1 vaccines based on regulatory proteins, such as Tat, are aimed at controlling HIV-1 replication and at blocking disease development by inducing cytotoxic T cell responses. Naked DNA is capable of inducing such responses but it requires several inoculations of high amounts of DNA, and/or prime-boost regimens. Here, we show that a novel class of cationic block copolymers protect the DNA from DNAse I digestion, and improve DNA delivery to antigen-presenting cells (APCs) after intramuscular (i.m.) vaccination. In particular, three cationic block copolymers (K1, K2 and K5) were used to deliver the HIV-1 pCV-tat DNA vaccine in BALB/c mice. The results indicate that vaccination with a very low dose (1 microg) of pCV-tat delivered by the cationic block copolymer K2 is safe and, as compared to naked DNA (up to 30 microg), greatly increases the CTL response against Tat, which was detected in all animals in the absence or in the presence of re-stimulation.
authors.affiliation: Department of Experimental and Diagnostic Medicine, Section of Microbiology, University of Ferrara, Via Luigi Borsari 46, I-44100 Ferrara, Italy. cpa@unife.it
authors.forename: Antonella
authors.initials: A
authors.lastname: Caputo
authors.forename: Riccardo
authors.initials: R
authors.lastname: Gavioli
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Altavilla
authors.forename: Egidio
authors.initials: E
authors.lastname: Brocca-Cofano
authors.forename: Chiara
authors.initials: C
authors.lastname: Boarini
authors.forename: Monica
authors.initials: M
authors.lastname: Betti
authors.forename: Arianna
authors.initials: A
authors.lastname: Castaldello
authors.forename: Franco
authors.initials: F
authors.lastname: Lorenzini
authors.forename: Fabiola
authors.initials: F
authors.lastname: Micheletti
authors.forename: Aurelio
authors.initials: A
authors.lastname: Cafaro
authors.forename: Katia
authors.initials: K
authors.lastname: Sparnacci
authors.forename: Michele
authors.initials: M
authors.lastname: Laus
authors.forename: Luisa
authors.initials: L
authors.lastname: Tondelli
authors.forename: Barbara
authors.initials: B
authors.lastname: Ensoli
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology; D000818:Animals; D000918:Antibody Specificity; D002412:Cations; D003692:Delayed-Action Preparations; D003850:Deoxyribonuclease I / Q000037:antagonists & inhibitors*; D004337:Drug Carriers; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D005347:Fibroblasts / Q000276:immunology; D015696:Gene Products, tat / Q000276:immunology*; D015756:Genes, tat; D015483:HIV Antibodies / Q000096:biosynthesis / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D007111:Immunity, Cellular; D007273:Injections, Intramuscular; D008213:Lymphocyte Activation; D008689:Methacrylates / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009757:Nylons / Q000494:pharmacology*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000494:pharmacology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D013154:Spleen / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology; D054322:tat Gene Products, Human Immunodeficiency Virus
chemical_list: D016915:AIDS Vaccines; D002412:Cations; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004791:Enzyme Inhibitors; D015696:Gene Products, tat; D015483:HIV Antibodies; D008689:Methacrylates; D009757:Nylons; D011993:Recombinant Fusion Proteins; D019444:Vaccines, DNA; C407037:poly(2-(dimethylamino)ethyl methacrylate); D054322:tat Gene Products, Human Immunodeficiency Virus; D011092:Polyethylene Glycols; D003850:Deoxyribonuclease I