No abstract

Tetrahymena thermophila has been transformed to paromomycin-resistant phenotypes by microinjec-

No abstract

cAdVAV 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 (LD 50 ) 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. Bacillus anthracis is a Gram-positive, rod-shaped, spore-forming bacterial pathogen and is the etiological agent of anthrax disease. Inhalation of the B. anthracis spores is associated with high levels of mortality in exposed individuals and has led to the use of aerosolized B. anthracis spores as a bioterror weapon (1-3). Following spore inhalation, B. anthracis undergoes a transformation from quiescent spores into a vegetative state associated with active growth and release of two binary toxins that mediate the majority of the pathological effects of anthrax disease. These toxins, lethal toxin and edema toxin, are formed through the interaction of lethal factor (LF) and edema factor (EF) with protective antigen (PA) (4). Vaccines against anthrax are not intended to inhibit B. anthracis vegetative growth but rather are directed against PA and the central role this protein plays in the pathogenesis of anthrax disease. Previous studies have shown that neutralizing antibody to PA is correlated with protection from anthrax disease (5-8).Vaccines derived from replication-deficient adenoviral vectors are deleted in E1 gene function, ensuring that replication can only be supported in specialized cell lines that provide the essential E1 function in trans. Frequently, one or more of the E3 gene products are also deleted in order to abolish the immunosuppressive activities of some E3 ge...

No abstract