DNA prime and protein boost immunization with innovative polymeric cationic core-shell nanoparticles elicits broad immune responses and strongly enhance cellular responses of HIV-1 tat DNA vaccination.
Novel biocompatible core-shell cationic nanoparticles, composed of an inner hard core of poly(methylmethacrylate) (PMMA) and a hydrophilic tentacular shell bearing positively charged groups and poly(ethyleneglycol) chains covalently bound to the core, were prepared by emulsion polymerization and characterized in vitro and in vivo for DNA vaccine applications. The nanoparticles reversibly adsorbed large amounts of DNA, mainly through electrostatic interactions, preserved its functional structure, efficiently delivered it intracellularly, and were not toxic in vitro or in mice. Furthermore, two intramuscular (i.m.) immunizations (4 weeks apart) with a very low dose (1 microg) of the plasmid pCV-tat delivered by these nanoparticles followed by one or two protein boosts induced significant antigen-specific humoral and cellular responses and greatly increased Th1-type T cell responses and CTLs against HIV-1 Tat.
Castaldello
Arianna
A
Department of Histology, Microbiology and Medical Biotechnology, Section of Microbiology, University of Padova, Via A. Gabelli 63, 35122 Padova, Italy.
Brocca-Cofano
Egidio
E
Voltan
Rebecca
R
Triulzi
Chiara
C
Altavilla
Giuseppe
G
Laus
Michele
M
Sparnacci
Katia
K
Ballestri
Marco
M
Tondelli
Luisa
L
Fortini
Cinzia
C
Gavioli
Riccardo
R
Ensoli
Barbara
B
Caputo
Antonella
A
D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000276:immunology; D000818:Animals; D002412:Cations / Q000008:administration & dosage / Q000276:immunology; D016503:Drug Delivery Systems; D005260:Female; D015696:Gene Products, tat / Q000235:genetics / Q000276:immunology*; D015483:HIV Antibodies / Q000097:blood; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D007115:Immunization Schedule; D007117:Immunization, Secondary / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D049329:Nanostructures / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000008:administration & dosage*; D019904:Polymethyl Methacrylate / Q000737:chemistry; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D014611:Vaccination; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000276:immunology; D054322:tat Gene Products, Human Immunodeficiency Virus
D016915:AIDS Vaccines; D002412:Cations; D015696:Gene Products, tat; D015483:HIV Antibodies; D011108:Polymers; D019444:Vaccines, DNA; D054322:tat Gene Products, Human Immunodeficiency Virus; D011092:Polyethylene Glycols; D019904:Polymethyl Methacrylate