Development of a Next Generation Anthrax Vaccine, dmPA7909

描述（由申请人提供）：Emergent BioSolutions Inc.（紧急）正在提议推进一种新型炭疽疫苗dmPA 7909的开发。这种下一代疫苗由双突变重组炭疽杆菌保护性抗原（dmPA）、铝佐剂Alhydrogel（r）和配制成干粉的免疫刺激性寡脱氧核苷酸化合物CPG 7909（Vaxlmmune（tm））组成。为了确保dmPA 7909疫苗即使在高温下也能保持稳定，Emergent对疫苗配方中的每种成分都采用了经过验证的稳定技术。dmPA经过基因工程改造，去除了分子内两个主要的蛋白酶切割位点，因此其稳定性显著提高。这种吸附在Alhydrogel上的稳定dmPA已在动物有效性研究中进行了测试，目前正与Alhydrogel联合用于1期临床试验。Alhydrogel（氢氧化铝）在疫苗（包括儿童疫苗）中具有悠久的使用历史，并记录了25和37 ℃下的稳定性。与其他CpG寡核苷酸不同，CPG 7909的所有磷酸酯键都被硫代磷酸酯键取代，因此降低了其对核酸酶的敏感性，从而使其稳定。此外，喷雾干燥的粉末制剂即使在极端温度下也能显著提高疫苗的稳定性。CPG 7909也已在临床上单独进行了广泛测试，并与其他含铝水凝胶佐剂的重组疫苗联合使用。dmPA 7909的特性使其成为满足国家对下一代炭疽疫苗需求的理想候选物：1。2-3剂后快速免疫反应2.长期稳定性，便于在环境温度下储存在国家战略储备3中。能够在国家紧急情况下进行管理，而无需特殊的储存条件

DESCRIPTION (provided by applicant): Emergent BioSolutions Inc. (Emergent) is proposing to advance the development of a novel anthrax vaccine dmPA7909. This next generation vaccine is composed of the double-mutant recombinant Bacillus anthracis protective antigen (dmPA), the aluminum adjuvant Alhydrogel(r) and the immunostimulatory oligodeoxynucleotide compound CPG 7909 (Vaxlmmune(tm)) formulated as a dry powder. To ensure that the dmPA7909 vaccine will be stable even at elevated temperatures, Emergent employed proven stabilizing technologies for each of the components in the vaccine formulation. The dmPA has been genetically engineered to remove two major protease cleavage sites within the molecule, and as a result, its stability is significantly improved. This stable dmPA adsorbed to Alhydrogel has been tested in animal efficacy studies and is currently being used in combination with Alhydrogel in a Phase 1 clinical trial. Alhydrogel (aluminum hydroxide) has a long history of use in vaccines including childhood vaccines and has documented stability at 25 and 37 ¿C. CPG 7909, unlike other CpG oligonucleotides, has all of its phosphate linkages replaced with phosphorothioate bonds, thus decreasing its sensitivity to nucleases, thus rendering it stable. Additionally, the spray-dried powder formulation dramatically enhances vaccine stability even at extreme temperatures for an extended period of time. CPG 7909 has also been extensively tested in the clinic alone, and in combination with other Alhydrogel-adjuvanted recombinant vaccines. The characteristics of dmPA7909 that make it an ideal candidate to meet the nation's needs for a next generation anthrax vaccine are: 1. Rapid immune response following 2-3 doses 2. Long-term stability to facilitate ambient temperature storage in the Strategic National Stockpile 3. Ability to be administered in a national emergency without the need for special storage conditions