Babiuk Shawn, Mookherjee Neeloffer, Pontarollo Reno, Griebel Phillip, van Drunen Littel-van den Hurk Sylvia, Hecker Rolf, Babiuk Lorne
Pyxis Genomics Canada, Saskatoon, Saskatchewan, Canada.
Immunology. 2004 Sep;113(1):114-20. doi: 10.1111/j.1365-2567.2004.01938.x.
Plasmid DNA continues to attract interest as a potential vaccine-delivery vehicle. However, the mechanisms whereby immune responses are elicited by plasmids are not fully understood. Although there have been suggestions regarding the importance of CpG motifs in plasmid immunogenicity, the molecular mechanisms by which CpG motifs enhance immune responses to DNA vaccines are not well understood. As Toll-like receptor 9-deficient (TLR9-/-) mice fail to respond to the adjuvant effects of CpG oligonucleotides, we used these mice to determine the effect of CpG motifs in plasmids used for DNA immunization. In the study described below, we report that DNA immunization was as effective in eliciting antigen-specific antibody and at stimulating antigen-specific interferon-gamma (IFN-gamma)-secreting cells in TLR9-/- mice as in TLR9+/+ mice. This study illustrates that DNA vaccines elicit immune responses by multiple mechanisms and demonstrates that TLR9 is not essential for the induction of immune responses following DNA immunization.
质粒DNA作为一种潜在的疫苗递送载体，持续吸引着人们的关注。然而，质粒引发免疫反应的机制尚未完全明确。尽管有人提出CpG基序在质粒免疫原性中的重要性，但CpG基序增强对DNA疫苗免疫反应的分子机制仍不清楚。由于Toll样受体9缺陷（TLR9-/-）小鼠对CpG寡核苷酸的佐剂效应无反应，我们利用这些小鼠来确定用于DNA免疫的质粒中CpG基序的作用。在如下所述的研究中，我们报告DNA免疫在TLR9-/-小鼠中引发抗原特异性抗体以及刺激抗原特异性分泌干扰素-γ（IFN-γ）细胞方面与在TLR9+/+小鼠中一样有效。本研究表明DNA疫苗通过多种机制引发免疫反应，并证明TLR9对于DNA免疫后诱导免疫反应并非必不可少。
