Immunization with low doses of HIV-1 tat DNA delivered by novel cationic block copolymers induces CTL responses against Tat.
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.
Caputo
Antonella
A
Department of Experimental and Diagnostic Medicine, Section of Microbiology, University of Ferrara, Via Luigi Borsari 46, I-44100 Ferrara, Italy. cpa@unife.it
Gavioli
Riccardo
R
Altavilla
Giuseppe
G
Brocca-Cofano
Egidio
E
Boarini
Chiara
C
Betti
Monica
M
Castaldello
Arianna
A
Lorenzini
Franco
F
Micheletti
Fabiola
F
Cafaro
Aurelio
A
Sparnacci
Katia
K
Laus
Michele
M
Tondelli
Luisa
L
Ensoli
Barbara
B
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
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