Nonhuman primate models and the failure of the Merck HIV-1 vaccine in humans
Nonhuman primate models and the failure of the Merck HIV-1 vaccine in humans
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DOI：
10.1038/nm.f.1759
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发表时间：
2008-06-01
期刊：
影响因子：
82.9
通讯作者：
Koff, Wayne C.
中科院分区：
文献类型：
--
作者：
Watkins, David I.;Burton, Dennis R.;Koff, Wayne C.
默克公司开发的基于5型腺病毒（Ad 5）的疫苗在STEP人体2b期疗效试验中未能预防HIV-1感染或抑制随后感染受试者的病毒载量。类似的疫苗以前也在猴免疫缺陷病毒（SIV）攻击恒河猴模型中失败。相比之下，在猕猴中使用嵌合猴-人类免疫缺陷病毒（SHIV89.6P）进行攻击的疫苗保护研究并没有预测人类试验结果。基于Ad 5载体的疫苗在SHIV89.6P攻击后不能保护猕猴免受感染，但确实引起病毒载量的显著降低和感染后CD 4（+）T细胞计数的保留，这一发现在人体试验中没有重现。虽然SIV挑战模型是不完全验证，我们建议，其扩大使用可以帮助促进候选HIV-1疫苗的优先顺序，确保资源集中在最有前途的候选人。疫苗设计者现在必须开发T细胞疫苗策略，以减少异源攻击后的病毒载量。
The adenovirus type 5 (Ad5)-based vaccine developed by Merck failed to either prevent HIV-1 infection or suppress viral load in subsequently infected subjects in the STEP human Phase 2b efficacy trial. Analogous vaccines had previously also failed in the simian immunodeficiency virus (SIV) challenge-rhesus macaque model. In contrast, vaccine protection studies that used challenge with a chimeric simian-human immunodeficiency virus (SHIV89.6P) in macaques did not predict the human trial results. Ad5 vector -based vaccines did not protect macaques from infection after SHIV89.6P challenge but did cause a substantial reduction in viral load and a preservation of CD4(+) T cell counts after infection, findings that were not reproduced in the human trials. Although the SIV challenge model is incompletely validated, we propose that its expanded use can help facilitate the prioritization of candidate HIV-1 vaccines, ensuring that resources are focused on the most promising candidates. Vaccine designers must now develop T cell vaccine strategies that reduce viral load after heterologous challenge.