A single immunization with a dry powder anthrax vaccine protects rabbits against lethal aerosol challenge.
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 150microg and therefore was chosen as the target dose for all subsequent experiments. Rabbits received a single dose of either 150microg rPA, 150microg rPA+150microg of a conjugated 10-mer peptide representing the Bacillus anthracis capsule (conj), or 150microg of conj alone. All dry powder formulations contained MPL and chitosan (ChiSys). 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.
Klas
S D
SD
LigoCyte Pharmaceuticals, Inc., 2155 Analysis Drive, Bozeman, MT 59718, United States. sheri.klas@ligocyte.com
Petrie
C R
CR
Warwood
S J
SJ
Williams
M S
MS
Olds
C L
CL
Stenz
J P
JP
Cheff
A M
AM
Hinchcliffe
M
M
Richardson
C
C
Wimer
S
S
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000281:Administration, Intranasal; D000336:Aerosols; D000534:Alum Compounds / Q000494:pharmacology; D000818:Animals; D000881:Anthrax / Q000276:immunology* / Q000517:prevention & control*; D022122:Anthrax Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D000907:Antibodies, Bacterial / Q000032:analysis / Q000096:biosynthesis; D000942:Antigens, Bacterial / Q000276:immunology; D016667:Bacterial Capsules / Q000276:immunology; D002626:Chemistry, Pharmaceutical; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007074:Immunoglobulin G / Q000032:analysis / Q000096:biosynthesis; D007202:Indicators and Reagents; D009500:Neutralization Tests; D011208:Powders; D011817:Rabbits; D012996:Solutions; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology
D000276:Adjuvants, Immunologic; D000336:Aerosols; D000534:Alum Compounds; D022122:Anthrax Vaccines; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D007074:Immunoglobulin G; D007202:Indicators and Reagents; D011208:Powders; D012996:Solutions; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic; C041524:aluminum sulfate