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）：我们已经表明，用展示来自保护性抗原（PA）结构域2的序列的多种抗原肽（MAP）免疫兔，可引发对保护性抗原（PA）结构域2内的线性决定簇特异性的抗体。 PA的2 β 2 - 2 β 3环，其在体外介导致死毒素（LeTx）的有效中和。我们现在已经在两项独立的大型研究中表明，针对该位点的抗体（称为环中和决定簇（LND））可以介导兔对200 LD 50靶剂量B雾化孢子吸入攻击的完全保护。炭疽艾姆斯菌株。LND特异性抗体不存在于兔PA抗血清中，更重要的是，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，因此代表了用于开发炭疽的独立或预防性疫苗的独特和新的特异性。我们现在已经使用我们的新型专有平台技术开发了优化的高免疫原性LND-VLP疫苗，该技术将疫苗靶序列并入高免疫原性病毒样颗粒中。这种新的LND疫苗，当与人类使用的佐剂配制时，有可能仅用一次或两次注射就引起针对炭疽的有效和快速的保护性免疫。在当前的项目中，我们将通过插入我们在致死因子中鉴定的第二线性中和表位来进一步优化LND-VLP疫苗，以在新的二价LND-LF-VLP疫苗中建立额外的关键冗余和增加的效力，这有望成为炭疽暴露前和暴露后的安全和战略性的新疫苗。