title: Efficacy and immunogenicity of single-dose AdVAV intranasal anthrax vaccine compared to anthrax vaccine absorbed in an aerosolized spore rabbit challenge model.
abstract: AdVAV is a replication-deficient adenovirus type 5-vectored vaccine expressing the 83-kDa protective antigen (PA83) from Bacillus anthracis that is being developed for the prevention of disease caused by inhalation of aerosolized B. anthracis spores. A noninferiority study comparing the efficacy of AdVAV to the currently licensed Anthrax Vaccine Absorbed (AVA; BioThrax) was performed in New Zealand White rabbits using postchallenge survival as the study endpoint (20% noninferiority margin for survival). Three groups of 32 rabbits were vaccinated with a single intranasal dose of AdVAV (7.5 × 10(7), 1.5 × 10(9), or 3.5 × 10(10) viral particles). Three additional groups of 32 animals received two doses of either intranasal AdVAV (3.5 × 10(10) viral particles) or intramuscular AVA (diluted 1:16 or 1:64) 28 days apart. The placebo group of 16 rabbits received a single intranasal dose of AdVAV formulation buffer. All animals were challenged via the inhalation route with a targeted dose of 200 times the 50% lethal dose (LD50) of aerosolized B. anthracis Ames spores 70 days after the initial vaccination and were followed for 3 weeks. PA83 immunogenicity was evaluated by validated toxin neutralizing antibody and serum anti-PA83 IgG enzyme-linked immunosorbent assays (ELISAs). All animals in the placebo cohort died from the challenge. Three of the four AdVAV dose cohorts tested, including two single-dose cohorts, achieved statistical noninferiority relative to the AVA comparator group, with survival rates between 97% and 100%. Vaccination with AdVAV also produced antibody titers with earlier onset and greater persistence than vaccination with AVA.
authors: Vaxin, Inc., Gaithersburg, Maryland, USA.
authors: Vyjayanthi
authors: V
authors: Krishnan
authors: Vaxin, Inc., Gaithersburg, Maryland, USA.
authors: Bo H
authors: BH
authors: Andersen
authors: Vaxin, Inc., Gaithersburg, Maryland, USA.
authors: Christine
authors: C
authors: Shoemaker
authors: Battelle Memorial Institute, Columbus, Ohio, USA.
authors: Gloria S
authors: GS
authors: Sivko
authors: Battelle Memorial Institute, Columbus, Ohio, USA.
authors: Kevin P
authors: KP
authors: Tordoff
authors: Battelle Memorial Institute, Columbus, Ohio, USA.
authors: Gregory V
authors: GV
authors: Stark
authors: Vaxin, Inc., Gaithersburg, Maryland, USA.
authors: Jianfeng
authors: J
authors: Zhang
authors: Vaxin, Inc., Gaithersburg, Maryland, USA.
authors: Tsungwei
authors: T
authors: Feng
authors: Genie Bio-Logic, Gaithersburg, Maryland, USA.
authors: Matthew
authors: M
authors: Duchars
authors: Vaxin, Inc., Gaithersburg, Maryland, USA sroberts@vaxin.com.
authors: M Scot
authors: MS
authors: Roberts
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000881:Anthrax / Q000276:immunology / Q000517:prevention & control*; D022122:Anthrax Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology*; D000907:Antibodies, Bacterial / Q000097:blood; D057134:Antibodies, Neutralizing / Q000097:blood; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D000992:Antitoxins / Q000097:blood; D001427:Bacterial Toxins / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D004337:Drug Carriers; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005822:Genetic Vectors; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D017921:Mastadenovirus / Q000235:genetics*; D009500:Neutralization Tests; D011817:Rabbits; D012141:Respiratory Tract Infections / Q000276:immunology / Q000517:prevention & control*; D016019:Survival Analysis; D014611:Vaccination / Q000379:methods; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D022122:Anthrax Vaccines; D000907:Antibodies, Bacterial; D057134:Antibodies, Neutralizing; D000942:Antigens, Bacterial; D000992:Antitoxins; D001427:Bacterial Toxins; D004337:Drug Carriers; D007074:Immunoglobulin G; D014614:Vaccines, Synthetic; C030325:anthrax toxin