Cytokine Response and Survival of Mice Immunized with an Adenovirus Expressing Bacillus anthracis Protective Antigen Domain 4

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Abstract
Adenovirus vectors are promising for use in vaccinating against potential agents of bioterrorism and emerging infections because of their proven safety in humans and their ability to elicit rapid immune responses. Here, we describe the construction and evaluation of an adenovirus vaccine expressing domain 4 of Bacillus anthracis protective antigen, Ad.D4. Ad.D4 elicited antibodies to protective antigen 14 days after a single intramuscular injection, which were further increased upon boosting. Furthermore, two doses of Ad.D4 4 weeks apart were sufficient to protect 67% of mice from toxin challenge. Additionally, we have characterized the release of inflammatory cytokines from vaccinated mice after lethal-toxin challenge. We demonstrate that interleukin 1β (IL-1β) levels in mice that survive lethal toxin challenge are similar to levels in nonsurvivors and that IL-6 levels are higher in survivors than in nonsurvivors. These findings suggest that lethal-toxin-mediated death may not be a direct result of inflammatory-cytokine release.