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.
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.
Voltan
Rebecca
R
Department of Histology, Microbiology and Medical Biotechnology, University of Padova, Padova, Italy.
Castaldello
Arianna
A
Brocca-Cofano
Egidio
E
De Michele
Rita
R
Triulzi
Chiara
C
Altavilla
Giuseppe
G
Tondelli
Luisa
L
Laus
Michele
M
Sparnacci
Katia
K
Reali
Eva
E
Gavioli
Riccardo
R
Ensoli
Barbara
B
Caputo
Antonella
A
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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