Journal
INFECTION AND IMMUNITY
Volume 74, Issue 2, Pages 1009-1015Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/IAI.74.2.1009-1015.2006
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Funding
- NCI NIH HHS [P30 CA046592, 5 P30 CA46592] Funding Source: Medline
- NIAID NIH HHS [R21 AI059231] Funding Source: Medline
- NIGMS NIH HHS [T32 GM07863, T32 GM145304, T32 GM008353, T32 GM007863, T32 GM08353] Funding Source: Medline
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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 1 beta (IL-1 beta) 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.
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