Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming 650118, China.
Vaccine. 2013 Jan 7;31(3):472-9. doi: 10.1016/j.vaccine.2012.11.024. Epub 2012 Nov 19.
Although the importance of DNA vaccines, especially as a priming immunization has been well established in numerous HIV vaccine studies, the immunogenictiy of DNA vaccines is generally moderate. Novel adjuvant is in urgent need for improving the immunogenicity of DNA vaccine. Polysaccharide and nucleic acid fraction extracted by hot phenol method from Mycobacterium bovis bacillus Calmette-Guérin, known as BCG-PSN, is a widely used immunomodulatory product in China clinical practice. In this study, we evaluated whether the BCG-PSN could serve as a novel adjuvant of DNA vaccine to trigger better cellular and humoral immune responses against the HIV-1 Env antigen in Balb/C mouse model. The BCG-PSN was mixed with 10 μg or 100 μg of pDRVI1.0gp145 (HIV-1 CN54 gp145 gene) DNA vaccine and intramuscularly immunized two or three times. We found that BCG-PSN could significantly improve the immunogenicity of DNA vaccine when co-administered with DNA vaccine. Further, at the same vaccination schedule, BCG-PSN co-immunization with 10 μg DNA vaccine could elicit cellular and humoral immune responses which were comparable to that induced by 100 μg DNA vaccine alone. Moreover, our results demonstrate that BCG-PSN can activate TLR signaling pathways and induce Th1-type cytokines secretion. These findings suggest that BCG-PSN can serve as a novel and effective adjuvant for DNA vaccination.
虽然 DNA 疫苗,尤其是作为初次免疫接种的重要性在许多 HIV 疫苗研究中已得到充分证实,但 DNA 疫苗的免疫原性通常较为温和。为了提高 DNA 疫苗的免疫原性,迫切需要新型佐剂。卡介苗多糖核酸(BCG-PSN)是从结核分枝杆菌提取的多糖和核酸混合物,通过热酚法提取,是中国临床实践中广泛使用的免疫调节剂。在本研究中,我们评估了 BCG-PSN 是否可以作为 DNA 疫苗的新型佐剂,以在 Balb/C 小鼠模型中引发针对 HIV-1 Env 抗原的更好的细胞和体液免疫反应。将 BCG-PSN 与 10μg 或 100μg pDRVI1.0gp145(HIV-1 CN54 gp145 基因)DNA 疫苗混合,肌肉内免疫 2 或 3 次。我们发现,BCG-PSN 与 DNA 疫苗联合使用时,可以显著提高 DNA 疫苗的免疫原性。此外,在相同的免疫接种方案下,BCG-PSN 与 10μg DNA 疫苗联合免疫可诱导出与单独使用 100μg DNA 疫苗相当的细胞和体液免疫反应。此外,我们的结果表明,BCG-PSN 可以激活 TLR 信号通路并诱导 Th1 型细胞因子的分泌。这些发现表明,BCG-PSN 可以作为 DNA 疫苗的新型有效佐剂。