Anthrax vaccine recipients lack antibody against the loop neutralizing determinant: A protective neutralizing epitope from Bacillus anthracis protective antigen.
Anthrax vaccine recipients lack antibody against the loop neutralizing determinant: A protective neutralizing epitope from Bacillus anthracis protective antigen.
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DOI：
10.1016/j.vaccine.2015.03.037
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发表时间：
2015-05-11
期刊：
影响因子：
5.5
通讯作者：
Cease KB
中科院分区：
文献类型：
--
作者：
Oscherwitz J;Quinn CP;Cease KB
抗原表位聚焦免疫原可诱导针对保护性抗原（PA）2β2-2β3环中的中和表位（LND）的抗体产生，该表位可保护家兔免受高剂量吸入攻击的炭疽杆菌艾姆斯菌株的攻击。有趣的是，数据表明该表位在用全长PA免疫的兔和非人灵长类动物中相对免疫沉默。为了确定在接种PA疫苗的人中LND是否是免疫沉默的，我们从临床试验中筛选来自AVA或安慰剂疫苗接种者的抗血清，以获得与LND反应的抗体。与安慰剂疫苗接种者血清相比，AVA疫苗接种者血清具有显著的PA特异性抗体;然而，就具有LND特异性抗体的个体的频率而言，来自两个队列的血清无法区分。AVA疫苗接种者与LND反应的抗体频率较低。与兔和非人灵长类动物一样，在人类中引发LND特异性抗体似乎需要用表位聚焦疫苗免疫。
Epitope-focused immunogens can elicit antibody against the loop neutralizing determinant (LND), a neutralizing epitope found within the 2β2-2β3 loop of protective antigen (PA), which can protect rabbits from high-dose inhalation challenge with Bacillus anthracis Ames strain. Interestingly, data suggests that this epitope is relatively immunosilent in rabbits and non-human primates immunized with full length PA. To determine whether the LND is immunosilent among humans vaccinated with PA, we screened antisera from AVA- or placebo-vaccinees from a clinical trial for antibody reactive with the LND. AVA-vaccinee sera had significant PA-specific antibody compared to placebo-vaccinee sera; however, sera from the two cohorts were indistinguishable with regard to the frequency of individuals with antibody specific for the LND. AVA-vaccinees have a low frequency of antibody reactive with the LND. As with rabbits and non-human primates, the elicitation of LND-specific antibody in humans appears to require immunization with an epitope-focused vaccine.