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: 8781529
• 负责人: JON OSCHERWITZ
• 金额: $ 26.02万
• 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 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8781529
• 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; Metric; 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; 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 2?2-2?3 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，具有多种抗原肽（MAP）的兔子的免疫接种，显示来自保护性抗原（PA）的域2的序列会引起对PA中2？2-2？3循环中的线性决定因素的特异性抗体，它介导致命的Toxin Toxin（Lethal Toxin）的中和中和抗体。现在，我们已经在两项单独的大型研究中表明，针对该部位的抗体（称为中和循环）的抗体（LND）可以通过200 LD50靶向的Anthracis Ames菌株的雾化孢子吸入挑战中完全保护兔子免受雾化的孢子吸入挑战。 LND特异性抗体不存在于兔Pa-antiserum中，更重要的是，在Ava-vaccinee Sera中不存在。因此，LND的特异性与PA抗血清中存在的特异性是非重叠的，因此代表了炭疽式或辅助疫苗开发的独特而新颖的特异性。现在，我们使用我们的新型专有平台技术开发了一种优化的高度免疫原性LND-VLP疫苗，该技术将疫苗靶序列融合到高度免疫原性病毒中。这种新的LND疫苗在用人使用佐剂配制时，有可能在只注射一次或两次注射炭疽病的炭疽病上有效和快速的保护性免疫。在当前项目中，我们将通过插入第二个线性中和表位，进一步优化LND-VLP疫苗，我们在致命因子中确定了，以建立额外的临界冗余性和增加的效力 新的二价LND-LF-VLP疫苗，有望成为一种安全，战略性的新型炭疽前和暴露后疫苗。