A molecularly targeted 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序列的多个抗原肽（MAPs）免疫兔子，可引发对2?2-2？3环的PA，介导致命毒素（LeTx）的体外有效中和。我们现在已经在两个独立的大型研究中表明，针对该位点的抗体，称为环中和决定因子（LND），可以介导完全保护家兔免受200 ld50靶向剂量炭疽芽孢杆菌Ames菌株雾化吸入攻击。在兔抗pa血清中不存在lnd特异性抗体，更重要的是，在ava疫苗血清中不存在lnd特异性抗体。因此，LND特异性与PA抗血清中存在的特异性不重叠，因此代表了开发单独或辅助炭疽疫苗的独特而新颖的特异性。我们现在利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，该疫苗将疫苗靶序列整合到高免疫原性病毒样颗粒中。这种新型LND疫苗在配制时与人用佐剂配合使用时，只需注射一两次，就有可能引发针对炭疽的有效和快速保护性免疫。在目前的项目中，我们将进一步优化LND-VLP疫苗，通过插入我们在致死因子中确定的第二个线性中和表位，以建立额外的关键冗余和增加的效力

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.