Storni Tazio, Ruedl Christiane, Schwarz Katrin, Schwendener Reto A, Renner Wolfgang A, Bachmann Martin F
Cytos Biotechnology AG, Schlieren-Zürich, Switzerland.
J Immunol. 2004 Feb 1;172(3):1777-85. doi: 10.4049/jimmunol.172.3.1777.
DNA rich in nonmethylated CG motifs (CpGs) greatly facilitates induction of immune responses against coadministered Ags. CpGs are therefore among the most promising adjuvants known to date. Nevertheless, CpGs are characterized by two drawbacks. They have unfavorable pharmacokinetics and may exhibit systemic side effects, including splenomegaly. We show in this study that packaging CpGs into virus-like particles (VLPs) derived from the hepatitis B core Ag or the bacteriophage Qbeta is a simple and attractive method to reduce these two problems. CpGs packaged into VLPs are resistant to DNase I digestion, enhancing their stability. In addition, and in contrast to free CpGs, packaging CpGs prevents splenomegaly in mice, without affecting their immunostimulatory capacity. In fact, vaccination with CpG-loaded VLPs was able to induce high frequencies of peptide-specific CD8(+) T cells (4-14%), protected from infection with recombinant vaccinia viruses, and eradicated established solid fibrosarcoma tumors. Thus, packaging CpGs into VLPs improves both their immunogenicity and pharmacodynamics.
富含非甲基化CG基序（CpGs）的DNA极大地促进了针对共同给药抗原的免疫反应的诱导。因此，CpGs是迄今为止已知的最有前景的佐剂之一。然而，CpGs有两个缺点。它们具有不良的药代动力学，并且可能表现出全身副作用，包括脾肿大。我们在本研究中表明，将CpGs包装到源自乙肝核心抗原或噬菌体Qβ的病毒样颗粒（VLPs）中是一种简单且有吸引力的方法，可以减少这两个问题。包装到VLPs中的CpGs对DNase I消化具有抗性，从而增强了它们的稳定性。此外，与游离CpGs不同，包装CpGs可防止小鼠脾肿大，而不影响其免疫刺激能力。事实上，用负载CpG的VLPs进行疫苗接种能够诱导高频率的肽特异性CD8(+) T细胞（4-14%），预防重组痘苗病毒感染，并根除已建立的实体纤维肉瘤肿瘤。因此，将CpGs包装到VLPs中可改善其免疫原性和药效学。
