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 (1 μg) 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 1 μg 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.
| Original language | English |
|---|---|
| Pages (from-to) | 4498-4507 |
| Number of pages | 10 |
| Journal | Vaccine |
| Volume | 27 |
| Issue number | 33 |
| DOIs | |
| Publication status | Published - Jul 16 2009 |
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Keywords
- Cationic block copolymers
- DNA vaccination
- Prime-boost
ASJC Scopus subject areas
- Immunology and Microbiology(all)
- Infectious Diseases
- Public Health, Environmental and Occupational Health
- veterinary(all)
- Molecular Medicine
Cite this
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. / Voltan, Rebecca; Castaldello, Arianna; Brocca-Cofano, Egidio; De Michele, Rita; Triulzi, Chiara; Altavilla, Giuseppe; Tondelli, Luisa; Laus, Michele; Sparnacci, Katia; Reali, Eva; Gavioli, Riccardo; Ensoli, Barbara; Caputo, Antonella.
In: Vaccine, Vol. 27, No. 33, 16.07.2009, p. 4498-4507.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - 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
AU - Voltan, Rebecca
AU - Castaldello, Arianna
AU - Brocca-Cofano, Egidio
AU - De Michele, Rita
AU - Triulzi, Chiara
AU - Altavilla, Giuseppe
AU - Tondelli, Luisa
AU - Laus, Michele
AU - Sparnacci, Katia
AU - Reali, Eva
AU - Gavioli, Riccardo
AU - Ensoli, Barbara
AU - Caputo, Antonella
PY - 2009/7/16
Y1 - 2009/7/16
N2 - 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 (1 μg) 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 1 μg 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.
AB - 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 (1 μg) 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 1 μg 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.
KW - Cationic block copolymers
KW - DNA vaccination
KW - Prime-boost
UR - http://www.scopus.com/inward/record.url?scp=67649321235&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=67649321235&partnerID=8YFLogxK
U2 - 10.1016/j.vaccine.2009.05.031
DO - 10.1016/j.vaccine.2009.05.031
M3 - Article
C2 - 19450649
AN - SCOPUS:67649321235
VL - 27
SP - 4498
EP - 4507
JO - Vaccine
JF - Vaccine
SN - 0264-410X
IS - 33
ER -