Mullen Gregory E D, Aebig Joan A, Dobrescu Gelu, Rausch Kelly, Lambert Lynn, Long Carole A, Miles Aaron P, Saul Allan
Malaria Vaccine Development Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 5640 Fishers Lane, Rockville, MD 20852, USA.
Vaccine. 2007 Jul 20;25(29):5343-7. doi: 10.1016/j.vaccine.2007.05.007. Epub 2007 May 25.
CpG oligodeoxynucleotides are potent immunostimulants. In this study, CPG 7909 was formulated with the recombinant Plasmodium falciparum protein AMA1-C1 adsorbed to Alhydrogel (aluminum hydroxide) and used to immunize mice. Mice receiving free CPG 7909 in a separate same site injection to the AMA1-C1/Alhydrogel had the same antibody responses as mice receiving AMA1-C1/Alhydrogel alone. For mice immunized with CPG 7909 bound to the AMA1-C1/Alhydrogel formulation, there was a bell shaped CPG 7909 dose-response curve with the highest antibody response co-incident with the concentration of CPG 7909 that saturated binding to the Alhydrogel. At a higher CPG 7909 dose where 74% was unbound, there was no enhancement of response over AMA1-C1/Alhydrogel alone. Our results suggest that the adjuvant effects of CpGs are optimal when adsorbed to Alhydrogel and highlight the need for careful characterization of the vaccine formulation.
CpG 寡脱氧核苷酸是强效免疫刺激剂。在本研究中,将 CPG 7909 与吸附于氢氧化铝佐剂(Alhydrogel)的重组恶性疟原虫蛋白 AMA1-C1 一起配制,并用于免疫小鼠。在与 AMA1-C1/Alhydrogel 不同部位单独注射游离 CPG 7909 的小鼠,其抗体反应与单独接受 AMA1-C1/Alhydrogel 的小鼠相同。对于用与 AMA1-C1/Alhydrogel 制剂结合的 CPG 7909 免疫的小鼠,存在一条钟形的 CPG 7909 剂量反应曲线,最高抗体反应与饱和结合到 Alhydrogel 的 CPG 7909 浓度一致。在较高的 CPG 7909 剂量下,74%未结合,与单独使用 AMA1-C1/Alhydrogel 相比,反应没有增强。我们的结果表明,CpG 吸附到 Alhydrogel 时其佐剂效果最佳,并强调了对疫苗制剂进行仔细表征的必要性。