title: Mucosal immunization with attenuated Salmonella enterica serovar Typhi expressing protective antigen of anthrax toxin (PA83) primes monkeys for accelerated serum antibody responses to parenteral PA83 vaccine.
abstract: 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], >1.3x10(3)), 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.
authors.affiliation: Center for Vaccine Development, Division of Geographic Medicine, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors.forename: James E
authors.initials: JE
authors.lastname: Galen
authors.forename: Magaly
authors.initials: M
authors.lastname: Chinchilla
authors.forename: Marcela F
authors.initials: MF
authors.lastname: Pasetti
authors.forename: Jin Yuan
authors.initials: JY
authors.lastname: Wang
authors.forename: Licheng
authors.initials: L
authors.lastname: Zhao
authors.forename: Ivonne
authors.initials: I
authors.lastname: Arciniega-Martinez
authors.forename: David J
authors.initials: DJ
authors.lastname: Silverman
authors.forename: Myron M
authors.initials: MM
authors.lastname: Levine
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D022122:Anthrax Vaccines / Q000276:immunology*; D000907:Antibodies, Bacterial / Q000096:biosynthesis* / Q000097:blood; D000942:Antigens, Bacterial / Q000276:immunology*; D001427:Bacterial Toxins / Q000276:immunology*; D004333:Drug Administration Routes; D005260:Female; D005818:Genetic Engineering; D007117:Immunization, Secondary; D007074:Immunoglobulin G / Q000097:blood / Q000145:classification; D008252:Macaca fascicularis; D008253:Macaca mulatta; D008297:Male; D009297:Nasal Mucosa / Q000276:immunology; D011897:Random Allocation; D012485:Salmonella typhi / Q000235:genetics / Q000276:immunology*; D014613:Vaccines, Attenuated / Q000276:immunology
chemical_list: D022122:Anthrax Vaccines; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D007074:Immunoglobulin G; D014613:Vaccines, Attenuated; C030325:anthrax toxin