Journal
VACCINE
Volume 26, Issue 43, Pages 5494-5502Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2008.07.062
Keywords
Anthrax; Protective antigen; Dry powder vaccine; Intranasal; Single dose vaccine
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Funding
- U.S. Army Medical Research and Material Command [DAMD 17-01-C-0040]
- NIH [VC1 A1067156-02]
- National Institute of Allergy and Infectious Diseases
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Here we confirm that intranasal (IN) dry powder anthrax vaccine formulations are able to protect rabbits against aerosol challenge 9 weeks after a single immunization. The optimum dose of rPA in our dry powder anthrax vaccine formulation in rabbits was experimentally determined to be 150 mu g and therefore was chosen as the target dose for all subsequent experiments. Rabbits received a single dose of either 150 mu g rPA, 150 mu g rPA + 150 mu g of a conjugated 10-mer peptide representing the Bacillus anthracis capsule (conj), or 150 mu g of conj alone. All dry powder formulations contained MPL and chitosan (ChiSys (R)). Significant anti-rPA titers and anthrax lethal toxin neutralizing antibody (TNA) levels were seen with both rPA containing vaccines, although rPA-specific IgG and TNA levels were reduced in rabbits immunized with rPA plus conj. Nine weeks after immunization, rabbits were exposed to a mean aerosol challenge dose of 278 LD50 of Ames spores. Groups immunized with rPA or with rPA + conj had significant increases in survivor proportions compared to the negative control group by Logrank test (p = 0.0001 and 0.003, respectively), and survival was not statistically different for the rPA and rPA + conj immunized groups (p = 0.63). These data demonstrate that a single immunization With Our dry powder anthrax vaccine can protect against a lethal aerosol spore challenge 9 weeks later. (C) 2008 Elsevier Ltd. All rights reserved.
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