Hung Jung-Tung, Tsai Yi-Chieh, Lin Wen-Der, Jan Jia-Tsrong, Lin Kun-Hsien, Huang Jing-Rong, Cheng Jing-Yan, Chen Ming-Wei, Wong Chi-Huey, Yu Alice L
Genomics Research Center, Academia Sinica, Taipei 115, Taiwan; Institute of Stem Cell and Translational Cancer Research, Chang Gung Memorial Hospital at Linkou, Taoyuan 333, Taiwan.
Genomics Research Center, Academia Sinica, Taipei 115, Taiwan.
Antiviral Res. 2014 Jul;107:110-8. doi: 10.1016/j.antiviral.2014.04.007. Epub 2014 Apr 29.
H5N1 influenza virus is a highly pathogenic virus, posing a pandemic threat. Previously, we showed that phenyl analogs of α-galactosylceramide (α-GalCer) displayed greater NKT stimulation than α-GalCer. Here, we examined the adjuvant effects of one of the most potent analogs, C34, on consensus hemagglutinin based DNA vaccine (pCHA5) for H5N1 virus. Upon intramuscular electroporation of mice with pCHA5 with/without various α-GalCer analogs, C34-adjuvanted group developed the highest titer against consensus H5 and more HA-specific IFN-γ secreting CD8 cells (203±13.5) than pCHA5 alone (152.6±13.7, p<0.05). Upon lethal challenge of NIBRG-14 virus, C34-adjuvanted group (84.6%) displayed higher survival rate than pCHA5 only group (46.1%). In the presence of C34 as adjuvant, the antisera displayed broader and greater neutralizing activities against virions pseudotyped with HA of clade 1, and 2.2 than pCHA5 only group. Moreover, to simulate an emergency response to a sudden H5N1 outbreak, we injected mice intramuscularly with single dose of a new consensus H5 (pCHA5-II) based on 1192 full-length H5 sequences, with C34 as adjuvant. The latter not only enhanced the humoral immune response and protection against virus challenge, but also broadened the spectrum of neutralization against pseudotyped HA viruses. Our vaccine strategy can be easily implemented for any H5N1 virus outbreak by single IM injection of a consensus H5 DNA vaccine based on updated HA sequences using C34 as an adjuvant.
H5N1流感病毒是一种高致病性病毒，构成了大流行威胁。此前，我们表明α-半乳糖神经酰胺（α-GalCer）的苯基类似物比α-GalCer表现出更强的NKT刺激作用。在此，我们研究了最有效的类似物之一C34对基于H5N1病毒共有血凝素的DNA疫苗（pCHA5）的佐剂效应。在用pCHA5联合或不联合各种α-GalCer类似物对小鼠进行肌肉电穿孔后，C34佐剂组针对共有H5产生的滴度最高，且分泌HA特异性IFN-γ的CD8细胞（203±13.5）比单独使用pCHA5组（152.6±13.7，p<0.05）更多。在用NIBRG-14病毒进行致死性攻击后，C34佐剂组（84.6%）的存活率高于仅使用pCHA5组（46.1%）。在存在C34作为佐剂的情况下，抗血清对以第1和2分支的HA假型化的病毒粒子表现出比仅使用pCHA5组更广泛和更强的中和活性。此外，为了模拟对H5N1突然爆发的应急反应，我们以C34作为佐剂，对小鼠肌肉注射单剂量基于1192个全长H5序列的新共有H5（pCHA5-II）。后者不仅增强了体液免疫反应和对病毒攻击的保护作用，还拓宽了对假型化HA病毒的中和谱。通过单次肌肉注射基于更新的HA序列并以C34作为佐剂的共有H5 DNA疫苗，我们的疫苗策略可轻松应用于任何H5N1病毒爆发。
