Development of a Next Generation Anthrax Vaccine, dmPA7909

描述（由申请人提供）：Emergent BioSolutions Inc. （Emergent）提议推进新型炭疽疫苗dmPA7909的开发。该新一代疫苗由双突变重组炭疽芽孢杆菌保护性抗原（dmPA）、铝佐剂醛水凝胶(r)和免疫刺激寡脱氧核苷酸化合物CPG 7909 （vaximmune (tm)）组成，制成干粉状。为了确保dmPA7909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成熟的稳定技术。dmPA通过基因工程去除分子内两个主要的蛋白酶裂解位点，因此其稳定性显著提高。这种稳定的dmPA吸附在醛水凝胶上，已经在动物功效研究中进行了测试，目前正在与醛水凝胶联合进行一期临床试验。醛水凝胶（氢氧化铝）在包括儿童疫苗在内的疫苗中有着悠久的使用历史，并记录了在25和37℃下的稳定性。CPG 7909与其他CPG寡核苷酸不同，其所有的磷酸键都被硫代磷酸键取代，从而降低了对核酸酶的敏感性，从而使其稳定。此外，即使在极端温度下延长一段时间，喷雾干燥粉末制剂也能显著提高疫苗的稳定性。CPG 7909也已在临床中单独进行了广泛的测试，并与其他醛水凝胶佐剂重组疫苗联合使用。dmPA7909的特点使其成为满足国家对下一代炭疽疫苗需求的理想候选者：1。2-3剂后快速免疫反应长期稳定性，以促进国家战略储备的环境温度储存。在国家紧急情况下无需特殊储存条件即可管理的能力

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