Development of a Next Generation Anthrax Vaccine, dmPA7909

描述(由申请人提供)：Emerent BioSolutions Inc.(Emerent)建议推进一种新型炭疽疫苗dmPA7909的开发。这种新一代疫苗由双突变重组炭疽杆菌保护性抗原(DMPA)、铝佐剂Alwater Gel(R)和免疫刺激寡核苷酸化合物CPG 7909(Vaxlmmune(Tm))组成，制成干粉。为了确保dmPA7909疫苗即使在高温下也能保持稳定，Emerent对疫苗配方中的每一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，去除了分子中两个主要的蛋白酶裂解位点，其稳定性得到了显著改善。这种稳定的DMPA被吸附到Alwater Gel上，已经在动物疗效研究中进行了测试，目前正与Alwater Gel联合用于一期临床试验。铝水凝胶(氢氧化铝)在疫苗中的使用历史悠久，包括儿童疫苗，并记录了在25℃和37℃下的稳定性。与其他CpG寡核苷酸不同的是，CpG 7909的所有磷键都被硫代磷酸键取代，因此降低了其对核酸酶的敏感性，从而使其稳定。此外，喷雾干燥粉剂即使在极端温度下也能在较长一段时间内显著增强疫苗的稳定性。CPG 7909也已经在临床上进行了广泛的测试，并与其他阿尔水凝胶佐剂重组疫苗一起进行了测试。DmPA7909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疫苗：1.2-3剂后快速免疫反应2.长期稳定，便于在国家战略储备中的环境温度储存3.能够在国家紧急情况下使用，而不需要特殊的储存条件

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