TY - JOUR
T1 - Mucosal immunization with attenuated Aalmonella enterica serovar typhi expressing protective antigen of anthrax toxin (PA83) primes monkeys for accelerated serum antibody responses to parenteral PA83 vaccine
AU - Galen, James E.
AU - Chinchilla, Magaly
AU - Pasetti, Marcela F.
AU - Jin, Yuan Wang
AU - Zhao, Licheng
AU - Arciniega-Martinez, Ivonne
AU - Silverman, David J.
AU - Levine, Myron M.
N1 - Funding Information:
Financial support: Mid-Atlantic Regional Center for Excellence for Biodefense and Emerging Infectious Research (cooperative agreement grant U54 AI57168 [to M.M.L.]); National Institutes of Health (NIH; grants R01 AI29471 [to M.M.L.] and R01 AI065760 [to M.F.P.]); National Institute of Allergy and Infectious Diseases, NIH (research contract NO1 AI25461 [to M.M.L.]).
PY - 2009/2/1
Y1 - 2009/2/1
N2 - Salmonella enterica serovar Typhi vaccine strain CVD 908-htrA was genetically engineered for stable plasmid-based expression of protective antigen of anthrax toxin (PA83) fused with the export protein ClyA (ClyA-PA83). The priming potential of CVD 908-htrA expressing ClyA-PA83 was assessed in 12 rhesus and 20 cynomolgus macaques that were immunized mucosally (i.e., intranasally) on days 0 and 14. A parenteral booster with purified PA83 plus alum was given to rhesus macaques on days 42 and 225; cynomolgus monkeys received a booster with either PA or licensed anthrax vaccine (BioThrax; Emergent Biosolutions) only one time, 3 months after priming. Monkeys primed with S. Typhi expressing ClyA-PA83 developed high levels of serum toxin-neutralization activity (TNA) antibodies (50% effective dose [ED50], >1.3 × 103), 7 days after receipt of the booster, whereas unprimed controls lacked serum TNA (ED50, 0). In nonhuman primates, the success of this anthrax vaccine strategy based on heterologous mucosal priming followed by a parenteral subunit vaccine booster paves the way for clinical trials.
AB - Salmonella enterica serovar Typhi vaccine strain CVD 908-htrA was genetically engineered for stable plasmid-based expression of protective antigen of anthrax toxin (PA83) fused with the export protein ClyA (ClyA-PA83). The priming potential of CVD 908-htrA expressing ClyA-PA83 was assessed in 12 rhesus and 20 cynomolgus macaques that were immunized mucosally (i.e., intranasally) on days 0 and 14. A parenteral booster with purified PA83 plus alum was given to rhesus macaques on days 42 and 225; cynomolgus monkeys received a booster with either PA or licensed anthrax vaccine (BioThrax; Emergent Biosolutions) only one time, 3 months after priming. Monkeys primed with S. Typhi expressing ClyA-PA83 developed high levels of serum toxin-neutralization activity (TNA) antibodies (50% effective dose [ED50], >1.3 × 103), 7 days after receipt of the booster, whereas unprimed controls lacked serum TNA (ED50, 0). In nonhuman primates, the success of this anthrax vaccine strategy based on heterologous mucosal priming followed by a parenteral subunit vaccine booster paves the way for clinical trials.
UR - http://www.scopus.com/inward/record.url?scp=58849119173&partnerID=8YFLogxK
U2 - 10.1086/596066
DO - 10.1086/596066
M3 - Artículo
SN - 0022-1899
VL - 199
SP - 326
EP - 335
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 3
ER -