Wagner Hermann
Institut für Medizinische Mikrobiologie, Immunologie und Hygiene, Technische Universität München, Germany.
Adv Drug Deliv Rev. 2009 Mar 28;61(3):243-7. doi: 10.1016/j.addr.2008.12.010. Epub 2009 Jan 11.
Compared to "live" vaccines the immunogenicity of "split" vaccines is notably poor, because exogeneous antigens (Ag) insufficiently access the MHC class I processing pathway needed for cross-presentation. Here we review our evidence that targeting ligands of endosomally expressed Toll-like Receptors (TLRs), together with exogeneous Ag to endosomes of dendritic cells (DCs) conveys immunogenicity to Ag similar in magnitude as "live" vaccines that produce Ag. We explored the consequences of enforced endocytosis of "Ag plus TLR ligands" either by crosslinking Ag and CpG-Oligonucleotides (CpG-Ag conjugates) or by co-encapsulating Ag plus endosomally expressed TLR ligands in biodegradable microspheres (MP). While both approaches equally well yielded in effective cross-priming of MHC class I restricted CD8 T effector cells, our data recommend MP as a generally applicable endosomal delivery device to vaccinate for protective and therapeutic CD4 and CD8 T cell immunity. Furthermore, our data suggest that functional inactivation of Foxp3(+) regulatory T cells further enhances the immunogenicity of "split vaccines".
与“活”疫苗相比，“裂解”疫苗的免疫原性明显较差，因为外源性抗原（Ag）无法充分进入交叉呈递所需的MHC I类加工途径。在此，我们回顾了相关证据，即靶向内体表达的Toll样受体（TLR）的配体，并将其与外源性Ag一起递送至树突状细胞（DC）的内体，可赋予Ag与产生Ag的“活”疫苗相似程度的免疫原性。我们通过交联Ag与CpG寡核苷酸（CpG-Ag偶联物）或通过将Ag与内体表达的TLR配体共包封于可生物降解微球（MP）中，探索了强制“Ag加TLR配体”内吞的后果。虽然这两种方法在有效交叉启动MHC I类限制性CD8 T效应细胞方面同样有效，但我们的数据推荐MP作为一种普遍适用的内体递送装置，用于接种以产生保护性和治疗性CD4和CD8 T细胞免疫。此外，我们的数据表明，Foxp3(+)调节性T细胞的功能失活可进一步增强“裂解疫苗”的免疫原性。
