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

Rebecca Voltan, Arianna Castaldello, Egidio Brocca-Cofano, Rita De Michele, Chiara Triulzi, Giuseppe Altavilla, Luisa Tondelli, Michele Laus, Katia Sparnacci, Eva Reali, Riccardo Gavioli, Barbara Ensoli, Antonella Caputo

Research output: Contribution to journalArticle

9 Citations (Scopus)

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 languageEnglish
Pages (from-to)4498-4507
Number of pages10
JournalVaccine
Volume27
Issue number33
DOIs
Publication statusPublished - Jul 16 2009

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composite polymers
antigens
Antigens
DNA
mice
dosage
Proteins
proteins
vaccination
Technology
Th1 Cells
DNA Vaccines
electrostatic interactions
application technology
recombinant vaccines
Static Electricity
humoral immunity
adjuvants
aqueous solutions
Immunization

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 journalArticle

Voltan, R, Castaldello, A, Brocca-Cofano, E, De Michele, R, Triulzi, C, Altavilla, G, Tondelli, L, Laus, M, Sparnacci, K, Reali, E, Gavioli, R, Ensoli, B & Caputo, A 2009, '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', Vaccine, vol. 27, no. 33, pp. 4498-4507. https://doi.org/10.1016/j.vaccine.2009.05.031
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. / 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. In: Vaccine. 2009 ; Vol. 27, No. 33. pp. 4498-4507.
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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.

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