Abstract

Prime-boost vaccination using plasmid DNA and replication-defective adenovirus vectors has emerged as a highly effective strategy for vaccinating against viral pathogens. However, its ability to provide protection against bacterial disease has never been assessed. Here we evaluate prime-boost vaccination approaches for immunizing against anthrax. We show that mice primed with DNA and boosted with an adenovirus vector, both expressing domain four of Bacillus anthracis protective antigen (PA), have higher antibody and toxin-neutralizing titers than mice immunized with either single modality alone. DNA-primed/adenovirus-boosted mice also had significantly higher antibody and toxin-neutralizing titers than mice immunized with Anthrax Vaccine Adsorbed. High levels of antigen-specific interferon-gamma-secreting cells were present in vaccinated mice indicating that a cell-mediated immune response had also been stimulated. Both DNA-primed/adenovirus-boosted and adenovirus-primed/adenovirus-boosted mice were fully protected from Sterne strain spore challenge. We also show that a single injection with an adenovirus vector-expressing domain four of PA can provide partial protection from spore challenge 2 weeks after immunization and full protection 3 weeks after immunization. These results demonstrate that adenovirus-based prime-boost vaccination can provide rapid protection from anthrax and that this approach may be an effective strategy for immunizing against bacterial as well as viral pathogens.