A molecularly targeted pre- and post-exposure vaccine for anthrax

炭疽暴露前和暴露后分子靶向疫苗

• 批准号: 8889624
• 负责人: JON OSCHERWITZ
• 金额: $ 24.96万
• 依托单位: VLP BIOTECH, INC.
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-10 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8889624
• 关键词: Adjuvant; Adverse effects; Aerosols; Alhydrogel; Animal Model; Anthrax Vaccines; Anthrax disease; Antibodies; Antigens; Bacillus anthracis; Benchmarking; Biothrax; Breathing; Clinical; Collaborations; Development; Dose; Drug Formulations; Engineering; Epitopes; Evaluation; Event; Exposure to; Foundations; General Population; Health; Human; Immune Sera; Immunity; Immunization; In Vitro; Incidence; Individual; Injection of therapeutic agent; Institute of Medicine (U.S.); Lead; Lethal Dose 50; Licensing; Mediating; Military Personnel; Mus; Oryctolagus cuniculus; Peptides; Population; Protocols documentation; Qualifying; Reproduction spores; Risk; Serum; Site; Specificity; Technology; Testing; Toxin; Vaccination; Vaccines; Virus-like particle; aerosolized; anthrax lethal factor; base; comparative; immunogenic; immunogenicity; in vivo; member; neutralizing antibody; next generation; nonhuman primate; novel; novel vaccines; phase 2 study; targeted sequencing; vaccine development

DESCRIPTION (provided by applicant): We have shown that immunization of rabbits with multiple antigenic peptides (MAPs) displaying sequence from domain 2 of protective antigen (PA) elicit antibodies specific for a linear determinant within the 2ß2-2ß3 loop of PA, that mediate potent neutralization of lethal toxin (LeTx) in vitro. We have now shown in two separate large studies that antibodies against this site, referred to as the loop neutralizing determinant (LND), can mediate complete protection of rabbits from an aerosolized spore inhalation challenge with a 200 LD50-targeted dose of B. anthracis Ames strain. LND-specific antibody is not present in rabbit PA-antiserum and more importantly, is not present in AVA-vaccinee sera. The LND specificity, therefore, is non-overlapping with the specificities present in PA antisera, and therefore represents a unique and novel specificity for development of a stand-alone or adjunctive vaccine for anthrax. We have now developed an optimized highly immunogenic LND-VLP vaccine using our novel proprietary platform technology which incorporates the vaccine target sequence into highly immunogenic virus like particles. This new LND vaccine, when formulated with human use adjuvants, has the potential to elicit potent and rapid protective immunity against anthrax with only one or two injections. In the current project, we will further optimize the LND-VLP vaccine through insertion of a second linear neutralizing epitope we have identified in lethal factor, to establish additional critical redundancy and increased potency in a new bivalent LND-LF-VLP vaccine, which promises to be a safe and strategic new pre- and post-exposure vaccine for anthrax.

描述（由申请人提供）：我们已经证明，用显示保护性抗原（PA）结构域 2 的序列的多种抗原肽（MAP）对兔子进行免疫接种，会引发对线性决定簇内的线性决定簇具有特异性的抗体。 PA 的 2ß2-2ß3 环，在体外介导致命毒素 (LeTx) 的有效中和 我们现在在两项独立的大型研究中显示，针对该位点的抗体（称为环中和决定簇 (LND)）可以介导完全保护。兔子体内不存在 200 LD50 目标剂量的炭疽芽孢杆菌 Ames 菌株的雾化孢子吸入攻击。更重要的是，PA 抗血清不存在于 AVA 疫苗血清中。因此，LND 特异性与 PA 抗血清中存在的特异性不重叠，因此代表了独立或单独的血清的开发的独特且新颖的特异性。我们现在使用我们新颖的专有平台技术开发了一种优化的高免疫原性 LND-VLP 疫苗，该技术将疫苗靶序列整合到高免疫原性病毒样颗粒中。当与人类使用佐剂配制时，只需注射一两次即可引发针对炭疽的强效和快速保护性免疫。在当前项目中，我们将通过插入我们拥有的第二个线性中和表位来进一步优化 LND-VLP 疫苗。确定致死因素，以在新型二价 LND-LF-VLP 疫苗中建立额外的关键冗余并增强效力，该疫苗有望成为一种安全且具有战略意义的新型炭疽暴露前和暴露后疫苗。