Successive site translocating inoculation potentiates DNA/recombinant vaccinia vaccination.
Successive site translocating inoculation potentiates DNA/recombinant vaccinia vaccination.
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DOI：
10.1038/srep18099
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发表时间：
2015-12-15
影响因子：
4.6
通讯作者：
Wan Y
中科院分区：
文献类型：
--
作者：
Ren Y;Wang N;Hu W;Zhang X;Xu J;Wan Y
DNA疫苗与传统疫苗方式相比具有优势；然而，相对较低的免疫原性限制了其转化为临床应用。需要进一步优化，使DNA疫苗的免疫原性更接近人类使用所需的水平。在这里，我们表明，与在同一肢体上重复接种疫苗相比，每次接种到不同肢体时，多次接种期间可显着提高 DNA 疫苗和重组牛痘疫苗的免疫原性。我们将这种策略称为连续位点易位接种（SSTI）。 SSTI 可以与遗传佐剂和 DNA 初免重组痘苗加强方案协同作用。通过比较体内抗原表达，我们发现SSTI避免了在重复接种的四肢中观察到的体内抗原表达的特异性抑制。利用体内 T 细胞耗竭和被动 IgG 转移，我们确定这种抑制不是由 CD8+ T 细胞介导的，而是由特异性抗体介导的。最后，通过使用 C3−/− 小鼠模型和体内 NK 细胞耗竭，我们发现特异性抗体主要以补体依赖性方式负调节体内抗原表达。
DNA vaccines have advantages over traditional vaccine modalities; however the relatively low immunogenicity restrains its translation into clinical use. Further optimizations are needed to get the immunogenicity of DNA vaccine closer to the level required for human use. Here we show that intramuscularly inoculating into a different limb each time significantly improves the immunogenicities of both DNA and recombinant vaccinia vaccines during multiple vaccinations, compared to repeated vaccination on the same limb. We term this strategy successive site translocating inoculation (SSTI). SSTI could work in synergy with genetic adjuvant and DNA prime-recombinant vaccinia boost regimen. By comparing in vivo antigen expression, we found that SSTI avoided the specific inhibition of in vivo antigen expression, which was observed in the limbs being repeatedly inoculated. Employing in vivo T cell depletion and passive IgG transfer, we delineated that the inhibition was not mediated by CD8+ T cells but by specific antibodies. Finally, by using C3−/− mouse model and in vivo NK cells depletion, we identified that specific antibodies negatively regulated the in vivo antigen expression primarily in a complement depended way.