AIDS and Cancer Virus Program, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland 21702, USA.
Division of Preventive and Behavioral Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA.
Nat Commun. 2017 Jun 5;8:15740. doi: 10.1038/ncomms15740.
Previous studies have shown that DNA prime, Ad5 boost vaccines protect against neutralization-sensitive but not neutralization-resistant virus variants within the SIVsmE660 swarm. Here we show that Ad prime, Env protein boost vaccines protect against neutralization-resistant SIVsmE660 variants. We perform two studies in rhesus monkeys with Ad35/Ad26 vectors expressing SIVmac239 Gag/Pol/Env with or without an AS01-adjuvanted SIVmac32H gp140 protein boost. In a repetitive, low-dose challenge study, we observe robust protection against acquisition of infection by both Ad Alone and Ad/Env vaccines. In a single, high-dose challenge study, only the Ad/Env vaccine affords significant protection against acquisition of infection. Analysis of transmitted/founder (T/F) viruses from this study demonstrates that the Ad/Env vaccine blocks both neutralization-sensitive and neutralization-resistant SIVsmE660 variants in rhesus monkeys with restrictive TRIM5α alleles. These data demonstrate that the adjuvanted Env protein boost is critical for protecting against high-dose SIVsmE660 challenge and for blocking neutralization-resistant viruses within the SIVsmE660 swarm.
先前的研究表明，DNA 初免、Ad5 增强疫苗可预防 SIVsmE660 群内对中和敏感但不对中和抗性的病毒变异株的感染。在此，我们展示了 Ad 初免、Env 蛋白增强疫苗可预防中和抗性的 SIVsmE660 变异株感染。我们在恒河猴中进行了两项研究，使用表达 SIVmac239 Gag/Pol/Env 的 Ad35/Ad26 载体，或用含有 AS01 佐剂的 SIVmac32H gp140 蛋白增强剂，进行 Ad 初免和 Ad 初免+Env 蛋白增强。在重复、低剂量的挑战研究中，我们观察到 Ad 初免和 Ad/Env 疫苗都能有效预防感染。在单次、高剂量的挑战研究中，只有 Ad/Env 疫苗可显著预防感染。从这项研究中分析传播/起源（T/F）病毒表明，Ad/Env 疫苗在具有限制性 TRIM5α 等位基因的恒河猴中可阻止对中和敏感和中和抗性的 SIVsmE660 变异株的感染。这些数据表明，增强的 Env 蛋白增强剂对于预防高剂量 SIVsmE660 挑战和阻止 SIVsmE660 群内中和抗性病毒至关重要。
