Epitope-focused peptide immunogens in human use adjuvants protect rabbits from experimental inhalation anthrax.
Epitope-focused peptide immunogens in human use adjuvants protect rabbits from experimental inhalation anthrax.
复制标题
人用佐剂中的针对表位的肽免疫原可以保护兔子免受实验性吸入性炭疽病的侵害。
DOI：
10.1016/j.vaccine.2014.11.042
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发表时间：
2015
期刊：
影响因子：
5.5
通讯作者：
Cease,KempB
中科院分区：
文献类型：
--
作者：
Oscherwitz,Jon;Feldman,Daniel;Yu,Fen;Cease,KempB
炭疽是一种可怕的生物恐怖主义威胁，需要新的优化疫苗。我们以前证明，表位集中的多抗原肽或弗氏佐剂中的重组蛋白可以引发针对环中和决定簇（LND）的Ab，LND是炭疽杆菌保护性抗原2 β 2 - 2 β 3环中的隐蔽线性中和表位，其介导了对B.炭疽菌然而，使用人类使用的佐剂的功效的证明是必需的，然后再进行进一步开发的LND疫苗在非人灵长类动物和human.MethodsTo优化LND免疫原，我们首先评估了保护性的功效和免疫相关性与免疫兔的混合物含有两种分子变异的多抗原肽的弗氏佐剂，称为BT-LND（2）和TB-LND（2）。结果用含TB-LND（2）的人用佐剂免疫家兔，可引起对艾姆斯菌株孢子攻击的保护作用，与用保护性抗原免疫的保护作用无统计学差异。所有在攻毒前具有任何可检测血清中和作用的TB-LND（2）家兔均受到保护，免于暴露于雾化孢子。值得注意的是，在Alhydrogel/CpG中用TB-LND（2）免疫的兔子在攻击后LND特异性Ab和中和滴度有显著的记忆增加，尽管这些兔子中孢子萌发的证据很少。
BackgroundAnthrax represents a formidable bioterrorism threat for which new, optimized vaccines are required. We previously demonstrated that epitope-focused multiple antigenic peptides or a recombinant protein in Freund's adjuvant can elicit Ab against the loop neutralizing determinant (LND), a cryptic linear neutralizing epitope in the 2ß2–2ß3 loop of protective antigen fromBacillus anthracis, which mediated protection of rabbits from inhalation challenge withB. anthracisAmes strain. However, demonstration of efficacy using human-use adjuvants is required before proceeding with further development of an LND vaccine for testing in non-human primates and humans.MethodsTo optimize the LND immunogen, we first evaluated the protective efficacy and immune correlates associated with immunization of rabbits with mixtures containing two molecular variants of multiple antigenic peptides in Freunds adjuvant, termed BT-LND(2) and TB-LND(2). TB-LND(2) was then further evaluated for protective efficacy in rabbits employing human-use adjuvants.ResultsImmunization of rabbits with TB-LND(2) in human-use adjuvants elicited protection from Ames strain spore challenge which was statistically indistinguishable from that elicited through immunization with protective antigen. All TB-LND(2) rabbits with any detectable serum neutralization prior to challenge were protected from aerosolized spore exposure. Remarkably, rabbits immunized with TB-LND(2) in Alhydrogel/CpG had significant anamnestic increases in post-challenge LND-specific Ab and neutralization titers despite little evidence of spore germination in these rabbits.ConclusionsAn LND-specific epitope-focused vaccine may complement PA-based vaccines and may represent a complementary stand-alone vaccine for anthrax.