State Key Laboratories for Agro-Biotechnology, College of Biological Science, China Agricultural University, Beijing, China.
J Gene Med. 2010 Jan;12(1):97-106. doi: 10.1002/jgm.1412.
Various approaches have been used to improve the efficacy of DNA vaccination, including the incorporation of molecular adjuvants. Because the CD40 ligand-CD40 interaction plays a major role in initiating immune responses, we sought to develop a molecular adjuvant targeting this interaction.
We immunized mice with a foot-and-mouth disease virus DNA vaccine, pcD-VP1, together with a CD40-expressing plasmid, pcD-CD40. We found that pcD-CD40 induced anti-CD40 antibodies, which temporally correlated with the augmented production of anti-VP1 antibody. pcD-CD40 similarly augmented the humoral response of another DNA vaccine that targets hepatitis B virus, and passive transfer of anti-CD40 antisera also showed a similar effect. Furthermore, the pcD-CD40-elicited anti-CD40 antibodies were able to activate the CD40 signal pathway in antigen-presenting cells in vitro, which led to the maturation of dendritic cells (DCs) and DC-mediated T cell activation. Thus, pcD-CD40 augments DNA vaccination by inducing anti-CD40 antibodies, which in turn promotes T cell activation.
This is the first reported 'proadjuvant' that augments DNA vaccination indirectly by eliciting agonistic antibodies.
为了提高 DNA 疫苗的效力，人们已经尝试了多种方法，包括加入分子佐剂。由于 CD40 配体-CD40 相互作用在启动免疫反应中起着重要作用，我们试图开发一种针对这种相互作用的分子佐剂。
我们用口蹄疫病毒 DNA 疫苗 pcD-VP1 与表达 CD40 的质粒 pcD-CD40 一起免疫小鼠。我们发现 pcD-CD40 诱导了抗 CD40 抗体，其产生与抗 VP1 抗体的增加呈时间相关性。pcD-CD40 同样增强了另一种针对乙型肝炎病毒的 DNA 疫苗的体液免疫反应，而抗 CD40 抗血清的被动转移也显示出类似的效果。此外，pcD-CD40 诱导的抗 CD40 抗体能够在体外激活抗原呈递细胞中的 CD40 信号通路，从而导致树突状细胞（DC）的成熟和 DC 介导的 T 细胞激活。因此，pcD-CD40 通过诱导抗 CD40 抗体来增强 DNA 疫苗接种，进而促进 T 细胞激活。
这是第一个报道的通过诱导激动性抗体间接增强 DNA 疫苗接种的“前佐剂”。
