title: Priming with a very low dose of DNA complexed with cationic block copolymers followed by protein boost elicits broad and long-lasting antigen-specific humoral and cellular responses in mice.
abstract: Cationic block copolymers spontaneously assemble via electrostatic interactions with DNA molecules in aqueous solution giving rise to micellar structures that protect the DNA from enzymatic degradation both in vitro and in vivo. In addition, we have previously shown that they are safe, not immunogenic and greatly increased antigen-specific CTL responses following six intramuscular inoculations of a very low dose (1microg) of the vaccine DNA as compared to naked DNA. Nevertheless, they failed to elicit detectable humoral responses against the antigen. To gain further insight in the potential application of this technology, here we show that a shorter immunization protocol based on two DNA intramuscular inoculations of 1microg of DNA delivered by these copolymers and a protein boost elicits in mice broad (both humoral and cellular) and long-lasting responses and increases the antigen-specific Th1-type T cell responses and CTLs as compared to priming with naked DNA. These results indicate that cationic block copolymers represent a promising adjuvant and delivery technology for DNA vaccination strategies aimed at combating intracellular pathogens.
authors.affiliation: Department of Histology, Microbiology and Medical Biotechnology, University of Padova, Padova, Italy.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Voltan
authors.forename: Arianna
authors.initials: A
authors.lastname: Castaldello
authors.forename: Egidio
authors.initials: E
authors.lastname: Brocca-Cofano
authors.forename: Rita
authors.initials: R
authors.lastname: De Michele
authors.forename: Chiara
authors.initials: C
authors.lastname: Triulzi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Altavilla
authors.forename: Luisa
authors.initials: L
authors.lastname: Tondelli
authors.forename: Michele
authors.initials: M
authors.lastname: Laus
authors.forename: Katia
authors.initials: K
authors.lastname: Sparnacci
authors.forename: Eva
authors.initials: E
authors.lastname: Reali
authors.forename: Riccardo
authors.initials: R
authors.lastname: Gavioli
authors.forename: Barbara
authors.initials: B
authors.lastname: Ensoli
authors.forename: Antonella
authors.initials: A
authors.lastname: Caputo
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology; D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D002412:Cations / Q000276:immunology; D049109:Cell Proliferation; D016207:Cytokines / Q000276:immunology; D018604:Epitope Mapping; D005260:Female; D015483:HIV Antibodies / Q000097:blood / Q000276:immunology; D015488:HIV Antigens / Q000276:immunology; D007111:Immunity, Cellular; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007273:Injections, Intramuscular; D051379:Mice; D008807:Mice, Inbred BALB C; D011108:Polymers / Q000494:pharmacology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D002412:Cations; D016207:Cytokines; D015483:HIV Antibodies; D015488:HIV Antigens; D007074:Immunoglobulin G; D011108:Polymers; D019444:Vaccines, DNA; D054322:tat Gene Products, Human Immunodeficiency Virus