Krishnan Vyjayanthi, Andersen Bo H, Shoemaker Christine, Sivko Gloria S, Tordoff Kevin P, Stark Gregory V, Zhang Jianfeng, Feng Tsungwei, Duchars Matthew, Roberts M Scot
Vaxin, Inc., Gaithersburg, Maryland, USA.
Battelle Memorial Institute, Columbus, Ohio, USA.
Clin Vaccine Immunol. 2015 Apr;22(4):430-9. doi: 10.1128/CVI.00690-14. Epub 2015 Feb 11.
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.
AdVAV是一种5型复制缺陷腺病毒载体疫苗，表达炭疽芽孢杆菌的83 kDa保护性抗原（PA83），正在研发用于预防吸入雾化炭疽芽孢杆菌孢子引起的疾病。在新西兰白兔中进行了一项非劣效性研究，比较AdVAV与目前已获许可的吸附型炭疽疫苗（AVA；BioThrax）的疗效，以攻毒后存活情况作为研究终点（存活的非劣效性 margin 为20%）。三组32只兔子经鼻内单剂量接种AdVAV（7.5×10⁷、1.5×10⁹或3.5×10¹⁰病毒颗粒）。另外三组32只动物在28天的间隔时间内分别接受两剂经鼻内接种的AdVAV（3.5×10¹⁰病毒颗粒）或肌肉注射的AVA（稀释1:16或1:64）。16只兔子的安慰剂组经鼻内单剂量接种AdVAV制剂缓冲液。所有动物在初次接种疫苗70天后通过吸入途径接受靶向剂量为雾化炭疽芽孢杆菌埃姆斯孢子50%致死剂量（LD50）200倍的攻毒，并观察3周。通过经过验证的毒素中和抗体和血清抗PA83 IgG酶联免疫吸附测定（ELISA）评估PA83免疫原性。安慰剂队列中的所有动物均死于攻毒。所测试的四个AdVAV剂量队列中的三个，包括两个单剂量队列，相对于AVA对照队列达到了统计学非劣效性，存活率在97%至100%之间。接种AdVAV产生的抗体滴度比接种AVA的起效更早且持续时间更长。
