title: Anthrax vaccine antigen-adjuvant formulations completely protect New Zealand white rabbits against challenge with Bacillus anthracis Ames strain spores.
abstract: In an effort to develop an improved anthrax vaccine that shows high potency, five different anthrax protective antigen (PA)-adjuvant vaccine formulations that were previously found to be efficacious in a nonhuman primate model were evaluated for their efficacy in a rabbit pulmonary challenge model using Bacillus anthracis Ames strain spores. The vaccine formulations include PA adsorbed to Alhydrogel, PA encapsulated in liposomes containing monophosphoryl lipid A, stable liposomal PA oil-in-water emulsion, PA displayed on bacteriophage T4 by the intramuscular route, and PA mixed with Escherichia coli heat-labile enterotoxin administered by the needle-free transcutaneous route. Three of the vaccine formulations administered by the intramuscular or the transcutaneous route as a three-dose regimen induced 100% protection in the rabbit model. One of the formulations, liposomal PA, also induced significantly higher lethal toxin neutralizing antibodies than PA-Alhydrogel. Even 5 months after the second immunization of a two-dose regimen, rabbits vaccinated with liposomal PA were 100% protected from lethal challenge with Ames strain spores. In summary, the needle-free skin delivery and liposomal formulation that were found to be effective in two different animal model systems appear to be promising candidates for next-generation anthrax vaccine development.
authors.affiliation: U.S. Military HIV Research Program, Henry M. Jackson Foundation for the Advancement of Military Medicine, Rockville, Maryland, USA.
authors.forename: Kristina K
authors.initials: KK
authors.lastname: Peachman
authors.forename: Qin
authors.initials: Q
authors.lastname: Li
authors.forename: Gary R
authors.initials: GR
authors.lastname: Matyas
authors.forename: Sathish B
authors.initials: SB
authors.lastname: Shivachandra
authors.forename: Julie
authors.initials: J
authors.lastname: Lovchik
authors.forename: Rick C
authors.initials: RC
authors.lastname: Lyons
authors.forename: Carl R
authors.initials: CR
authors.lastname: Alving
authors.forename: Venigalla B
authors.initials: VB
authors.lastname: Rao
authors.forename: Mangala
authors.initials: M
authors.lastname: Rao
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000279:Administration, Cutaneous; D000818:Animals; D000881:Anthrax / Q000517:prevention & control*; D022122:Anthrax Vaccines / Q000008:administration & dosage / Q000276:immunology*; D000907:Antibodies, Bacterial; D057134:Antibodies, Neutralizing / Q000097:blood; D000942:Antigens, Bacterial / Q000276:immunology*; D000992:Antitoxins / Q000097:blood; D001408:Bacillus anthracis / Q000276:immunology*; D001427:Bacterial Toxins / Q000008:administration & dosage; D017122:Bacteriophage T4; D004195:Disease Models, Animal; D004768:Enterotoxins / Q000008:administration & dosage; D029968:Escherichia coli Proteins / Q000008:administration & dosage; D005260:Female; D007273:Injections, Intramuscular; D008081:Liposomes / Q000008:administration & dosage; D053758:Nanoparticles / Q000008:administration & dosage; D011817:Rabbits; D016019:Survival Analysis; D013997:Time Factors
chemical_list: D000276:Adjuvants, Immunologic; D022122:Anthrax Vaccines; D000907:Antibodies, Bacterial; D057134:Antibodies, Neutralizing; D000942:Antigens, Bacterial; D000992:Antitoxins; D001427:Bacterial Toxins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D008081:Liposomes; C027538:heat-labile enterotoxin, E coli
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