Immunization with low doses of HIV-1 tat DNA delivered by novel cationic block copolymers induces CTL responses against Tat

• Published in: Vaccine 2003-03, Vol.21 (11), p.1103-1111
• Main Authors: Caputo, Antonella, Gavioli, Riccardo, Altavilla, Giuseppe, Brocca-Cofano, Egidio, Boarini, Chiara, Betti, Monica, Castaldello, Arianna, Lorenzini, Franco, Micheletti, Fabiola, Cafaro, Aurelio, Sparnacci, Katia, Laus, Michele, Tondelli, Luisa, Ensoli, Barbara
• Format: Article
• Language: English
• Subjects: AIDS Vaccines - immunology; Animals; Antibody Specificity; Biological and medical sciences; Cationic block copolymers; Cations; Delayed-Action Preparations; Deoxyribonuclease I - antagonists & inhibitors; Drug Carriers; Enzyme Inhibitors - pharmacology; Female; Fibroblasts - immunology; Fundamental and applied biological sciences. Psychology; Gene Products, tat - immunology; Genes, tat; HIV Antibodies - biosynthesis; HIV Antibodies - immunology; HIV-1 - immunology; HIV-1 tat gene; Human immunodeficiency virus 1; Human viral diseases; Immunity, Cellular; Infectious diseases; Injections, Intramuscular; Lymphocyte Activation; Medical sciences; Methacrylates - administration & dosage; Methacrylates - pharmacology; Mice; Mice immunization; Mice, Inbred BALB C; Microbiology; Nylons - pharmacology; Polyethylene Glycols - administration & dosage; Polyethylene Glycols - pharmacology; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - immunology; Spleen - immunology; T-Lymphocytes, Cytotoxic - immunology; tat Gene Products, Human Immunodeficiency Virus; Transfection; Vaccination; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies; Vaccines, DNA - immunology; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Virology
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/S0264-410X(02)00555-8

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 μg) of pCV- tat delivered by the cationic block copolymer K2 is safe and, as compared to naked DNA (up to 30 μg), greatly increases the CTL response against Tat, which was detected in all animals in the absence or in the presence of re-stimulation.