Immune correlates of protection against yellow fever determined by passive immunization and challenge in the hamster model
Immune correlates of protection against yellow fever determined by passive immunization and challenge in the hamster model
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DOI：
10.1016/j.vaccine.2011.06.034
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发表时间：
2011-08-11
期刊：
影响因子：
5.5
通讯作者：
Monath, Thomas P.
中科院分区：
文献类型：
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作者：
Julander, Justin G.;Trent, Dennis W.;Monath, Thomas P.
黄热病 (YF) 17D 减毒活疫苗非常有效，但由于在宿主体内的活跃复制和对重要器官的直接病毒损伤，会导致罕见的严重不良事件。我们最近报道了一种可能更安全的 β-丙内酯灭活全病毒粒子 YF 疫苗 (XRX-001) 的开发，该疫苗在小鼠、仓鼠、猴子和人类中具有高度免疫原性 [10,11]。为了表征灭活疫苗刺激的中和抗体的保护功效，在强毒、亲内脏的 YF 病毒攻击前 24 小时，通过腹膜内 (IP) 途径将来自用灭活 XRX-001 或活 170 疫苗免疫的仓鼠的分级剂量血清转移至仓鼠。在攻击前4小时以及攻击后4天和21天测定处理动物的血清中的中和抗体(PRNT(50))滴度。中和抗体被证明可以介导保护作用。攻击前4小时50%斑块减少中和试验（PRNT50）滴度≥40的动物完全免受疾病影响，如病毒血症、肝酶升高以及针对疾病（体重变化）和死亡的保护所证明的。 10-20 的被动滴度具有部分保护作用。 XRX-001 疫苗免疫刺激了 YF 中和抗体，其与活 17D 疫苗刺激的抗体同样有效（基于剂量反应）。研究结果将有助于确定新型黄热病疫苗临床研究中的血清保护水平。 (C) 2011 Elsevier Ltd. 保留所有权利。
Live, attenuated yellow fever (YF) 17D vaccine is highly efficacious but causes rare, serious adverse events resulting from active replication in the host and direct viral injury to vital organs. We recently reported development of a potentially safer beta-propiolactone-inactivated whole virion YFvaccine (XRX-001), which was highly immunogenic in mice, hamsters, monkeys, and humans [10,11]. To characterize the protective efficacy of neutralizing antibodies stimulated by the inactivated vaccine, graded doses of serum from hamsters immunized with inactivated XRX-001 or live 170 vaccine were transferred to hamsters by the intraperitoneal (IP) route 24 h prior to virulent, viscerotropic YF virus challenge. Neutralizing antibody (PRNT(50)) titers were determined in the sera of treated animals 4 h before challenge and 4 and 21 days after challenge. Neutralizing antibodies were shown to mediate protection. Animals having 50% plaque reduction neutralization test (PRNT50) titers of >= 40 4 h before challenge were completely protected from disease as evidenced by viremia, liver enzyme elevation, and protection against illness (weight change) and death. Passive titers of 10-20 were partially protective. Immunization with the XRX-001 vaccine stimulated YF neutralizing antibodies that were equally effective (based on dose response) as antibodies stimulated by live 17D vaccine. The results will be useful in defining the level of seroprotection in clinical studies of new yellow fever vaccines. (C) 2011 Elsevier Ltd. All rights reserved.