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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >A cationic lipid-formulated plasmid DNA vaccine confers sustained anti body-mediated protection against aerosolized anthrax spores
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A cationic lipid-formulated plasmid DNA vaccine confers sustained anti body-mediated protection against aerosolized anthrax spores

机译：阳离子脂质配制的质粒DNA疫苗可提供持续的抗体介导的抗气雾化炭疽孢子的保护作用

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摘要

DNA vaccines provide an attractive technology platform against bioterrorism agents due to their safety record in humans and ease of construction, testing, and manufacture. We have designed monovalent and bivalent anthrax plasmid DNA (pDNA) vaccines encoding genetically detoxified protective antigen (PA) and lethal factor (LF) proteins and tested their immunogenicity and ability to protect rabbits from an aerosolized inhalation spore challenge. Immune responses after two or three injections of cationic lipid-formulated PA, PA plus LF, or LF pDNAs were at least equivalent to two doses of anthrax vaccine adsorbed (AVA). High titers of anti-PA, anti-LF, and neutralizing antibody to lethal toxin (Letx) were achieved in all rabbits. Eight or nine animals in each group were challenged with 100x LD50 of aerosolized anthrax spores 5 or 9 weeks after vaccination. An additional 10 animals vaccinated with PA pDNA were challenged >7 months postvaccination. All animals receiving PA or PA plus LF pDNA vaccines were protected. In addition, 5 of 9 animals receiving LF pDNA survived, and the time to death was significantly delayed in the others. Groups receiving three immunizations with PA or PA plus LF pDNA showed no increase in anti-PA, anti-LF, or Letx neutralizing antibody titers postchallenge, suggesting little or no spore germination. In contrast, titer increases were seen in AVA animals, and in surviving animals vaccinated with LF pDNA alone. Preclinical evaluation of this cationic lipid-formulated bivalent PA and LF vaccine is complete, and the vaccine has received U.S. Food and Drug Administration Investigational New Drug allowance.
机译：由于DNA疫苗在人类中的安全记录以及易于构建，测试和制造的特性，因此DNA疫苗为抗生物恐怖分子提供了一个有吸引力的技术平台。我们设计了编码基因解毒的保护性抗原（PA）和致死因子（LF）蛋白的单价和二价炭疽质粒DNA（pDNA）疫苗，并测试了它们的免疫原性和保护兔子免受雾化吸入孢子攻击的能力。两次或三次注射阳离子脂质配制的PA，PA加LF或LF pDNA的免疫反应至少等于两剂吸附的炭疽疫苗（AVA）。在所有兔子中均获得了高滴度的抗PA，抗LF和中和性抗体，可抵抗致命毒素（Letx）。疫苗接种后5或9周，每组八或九只动物用100x LD50的雾化炭疽气孢子攻击。接种疫苗后> 7个月，对另外10只接种了PA pDNA的动物进行了攻击。所有接受PA或PA加LF pDNA疫苗的动物均受到保护。此外，接受LF pDNA的9只动物中有5只存活下来，其他动物的死亡时间明显延迟。接受PA或PA加LF pDNA三种免疫接种的组在攻击后抗PA，抗LF或Letx中和抗体滴度没有增加，表明孢子萌发很少或没有。相反，在AVA动物和仅接种LF pDNA的存活动物中，滴度增加。对该阳离子脂质配制的二价PA和LF疫苗的临床前评估已经完成，该疫苗已获得美国食品和药物管理局的新药研究许可。

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