Centre for Immune Regulation, Institute of Immunology, University of Oslo and Oslo University Hospital, Oslo, Norway.
Vaccine. 2010 Dec 16;29(2):191-9. doi: 10.1016/j.vaccine.2010.10.057. Epub 2010 Nov 4.
Efficacy of DNA vaccination has been improved in mice by fusion vaccines targeting antigen to antigen-presenting cells (APC) via chemokine receptors. Here, we aimed at extending this strategy to large animals and humans. Fusion proteins equipped with human MIP1α (LD78β isoform) retained functional activity and conformational correctness of targeting and antigenic units, respectively. Fusion proteins improved responses of cloned human CD4+ T cells, and a two amino acid NH(2)-truncated version of LD78β outperformed full length LD78β-vaccine proteins in vitro. LD78β DNA fusion vaccines induced improved T cell (both CD4+ and CD8+) and antibody responses in mice following plasmid injection and skin electroporation. Finally, LD78β-vaccine proteins bound Rhesus macaque CCR5, setting the stage for targeted DNA immunization in non-human primates.
通过趋化因子受体将抗原靶向抗原呈递细胞 (APC) 的融合疫苗提高了 DNA 疫苗在小鼠中的功效。在这里，我们旨在将该策略扩展到大型动物和人类。融合蛋白配备有人源 MIP1α（LD78β 同工型），分别保留了靶向和抗原单位的功能活性和构象正确性。融合蛋白改善了克隆的人类 CD4+ T 细胞的反应，并且 LD78β 的两个氨基酸 NH2-截断版本在体外优于全长 LD78β-疫苗蛋白。LD78β DNA 融合疫苗在质粒注射和皮肤电穿孔后，在小鼠中诱导了改善的 T 细胞（CD4+ 和 CD8+）和抗体反应。最后，LD78β-疫苗蛋白结合恒河猴 CCR5，为非人类灵长类动物的靶向 DNA 免疫奠定了基础。
