Vaccine and Infectious Disease Organization, University of Saskatchewan, 120 Veterinary Road, Saskatoon, Saskatchewan S7N 5E3, Canada.
Vaccine. 2010 Apr 9;28(17):2945-56. doi: 10.1016/j.vaccine.2010.02.015. Epub 2010 Mar 1.
Host defence peptides (HDPs) have a variety of potential therapeutic applications, including as vaccine adjuvants, energizing efforts for modification strategies to address their toxicity and instability. Here we compare l, d and RI-Bac2A as vaccine adjuvants. d and RI-Bac2A are equally resistant to proteolytic degradation with no increases in toxicity, however, only RI-Bac2A maintains adjuvant activity of the natural peptide through conserved induction of a Th2 immune response. As HDPs potentiate the adjuvant activity of CpG ODNs, the isomers were also evaluated as co-adjuvants. l-Bac2A has no significant co-adjuvant activity while CpG/RI-Bac2A induces antibody titres significantly higher than CpG (P<0.01), CpG/l-Bac2A (P<0.01) or CpG/d-Bac2A (P<0.01). None of the isomers influence ODN duration or distribution but l and RI-Bac2A promote ODN uptake into B cells and antigen presenting cells. The enhanced adjuvant and co-adjuvant of RI-Bac2A is hypothesized to result from an undefined combination of increased stability and retained biological activity supporting application of retro-inversion to this, and potentially other HDPs.
宿主防御肽 (HDPs) 具有多种潜在的治疗应用，包括作为疫苗佐剂，激发修改策略的努力以解决其毒性和不稳定性。在这里，我们将 l、d 和 RI-Bac2A 进行比较，作为疫苗佐剂。d 和 RI-Bac2A 对蛋白水解降解具有同等的抗性，没有增加毒性，然而，只有 RI-Bac2A 通过保守诱导 Th2 免疫反应来维持天然肽的佐剂活性。由于 HDPs 增强了 CpG ODN 的佐剂活性，因此还评估了这些异构体作为共佐剂。l-Bac2A 没有显著的共佐剂活性，而 CpG/RI-Bac2A 诱导的抗体滴度明显高于 CpG（P<0.01）、CpG/l-Bac2A（P<0.01）或 CpG/d-Bac2A（P<0.01）。这些异构体都不会影响 ODN 的持续时间或分布，但 l 和 RI-Bac2A 促进 ODN 进入 B 细胞和抗原呈递细胞的摄取。RI-Bac2A 的增强佐剂和共佐剂作用可能归因于稳定性增加和保留生物活性的未知组合，这支持将反转录应用于 RI-Bac2A 以及其他潜在的 HDPs。
