Granulocyte-macrophage colony-stimulating factor DNA prime-protein boost strategy to enhance efficacy of a recombinant pertussis DNA vaccine

Acta Pharmacol Sin. 2006 Nov;27(11):1487-94. doi: 10.1111/j.1745-7254.2006.00456.x.

Abstract

Aim: To investigate a new strategy to enhance the efficacy of a recombinant pertussis DNA vaccine. The strategy is co-injection with cytokine plasmids as prime, and boosted with purified homologous proteins.

Method: A recombinant pertussis DNA vaccine containing the pertussis toxin subunit 1 (PTS1), fragments of the filamentous hemagglutinin (FHA) gene and pertactin (PRN) gene encoding filamentous hemagglutinin and pertactin were constructed. Balb/c mice were immunized with several DNA vaccines and antigen-specific antibodies anti-PTS1,anti-PRN, anti-FHA,cytokines interleukin (IL)-10, IL-4, IFN-gamma,TNF-alpha,and splenocyte-proliferation assay were used to describe immune responses.

Results: The recombinant DNA vaccine could elicit similar immune responses in mice as that of separate plasmids encoding the 3 fragments, respectively. Mice immunized with DNA and boosted with the corresponding protein elicited more antibodies than those that received DNA as boost. In particular, when the mice were co-immunized with murine granulocyte-macrophage colony-stimulating factor plasmids and boosted with proteins, all 4 cytokines and the 3 antigen-specific antibodies were significantly increased compared to the pVAX1 group. Anti-PTS1, anti- FHA, IL-4 and TNF-alpha elicited in the colony stimulating factor (CSF) prime-protein boost group showed significant increase compared to all the other groups.

Conclusion: This prime and boost strategy has proven to be very useful in improving the immunogenicity of DNA vaccines against pertussis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Bacterial / metabolism
  • Bacterial Outer Membrane Proteins / genetics
  • Bacterial Outer Membrane Proteins / immunology
  • Bordetella pertussis / immunology*
  • Cell Proliferation
  • Cytokines / metabolism
  • DNA Primers
  • Granulocyte-Macrophage Colony-Stimulating Factor / genetics
  • Granulocyte-Macrophage Colony-Stimulating Factor / immunology*
  • Hemagglutinins / genetics
  • Hemagglutinins / immunology
  • Immunization
  • Mice
  • Mice, Inbred BALB C
  • Pertussis Toxin / genetics
  • Pertussis Toxin / immunology
  • Pertussis Vaccine / administration & dosage*
  • Pertussis Vaccine / immunology
  • Recombinant Proteins / genetics
  • Recombinant Proteins / immunology
  • Spleen / cytology
  • Vaccines, DNA / administration & dosage*
  • Vaccines, DNA / immunology
  • Virulence Factors, Bordetella / genetics
  • Virulence Factors, Bordetella / immunology

Substances

  • Antibodies, Bacterial
  • Bacterial Outer Membrane Proteins
  • Cytokines
  • DNA Primers
  • Hemagglutinins
  • Pertussis Vaccine
  • Recombinant Proteins
  • Vaccines, DNA
  • Virulence Factors, Bordetella
  • pertussis toxin, S1 subunit
  • pertactin
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Pertussis Toxin