Novartis Vaccines and Diagnostics, Cambridge, Massachusetts 02139, USA.
J Pharm Sci. 2011 Feb;100(2):646-54. doi: 10.1002/jps.22306.
This study evaluated the feasibility of using γ-irradiation for preparing sterile poly(lactide-co-glycolide) (PLG) formulations for vaccines. PLG microparticles were prepared by water-in-oil-in-water double-emulsion technique and lyophilized. The vials were γ-irradiated for sterilization process. Antigens from Neisseria meningitidis were adsorbed onto the surface of the particles and were characterized for protein adsorption. Antigens adsorbed onto the surface of the irradiated particles within 30 min. Mice were immunized with these formulations, and vaccine potency was measured as serum bactericidal titers. The γ-irradiated PLG particles resulted in equivalent serum bactericidal titers against a panel of five N. meningitidis strains as the nonirradiated PLG particles. The use of PLG polymers with different molecular weights did not influence the vaccine potency. The PLG particles prepared by γ-irradiation of the lyophilized formulations replace the need for aseptic manufacturing of vaccine formulations. This approach may enable the use of PLG formulations with a variety of antigens and stockpiling for pandemics.
本研究评估了使用γ射线辐照制备用于疫苗的无菌聚（乳酸-共-乙醇酸）（PLG）制剂的可行性。PLG 微球通过水包油包水双乳液技术制备并冻干。小瓶进行γ射线辐照以进行灭菌处理。脑膜炎奈瑟菌的抗原吸附到颗粒表面，并对其进行蛋白质吸附表征。抗原在 30 分钟内吸附到辐照颗粒的表面上。用这些制剂对小鼠进行免疫接种，并测量血清杀菌滴度作为疫苗效力。与未辐照的 PLG 颗粒相比，辐照的 PLG 颗粒对五种脑膜炎奈瑟菌菌株的血清杀菌滴度相当。使用不同分子量的 PLG 聚合物不会影响疫苗效力。通过辐照冻干制剂制备的 PLG 颗粒替代了疫苗制剂无菌制造的需求。这种方法可能使具有各种抗原的 PLG 制剂得以使用，并为大流行做好储备。
