Huckriede Anke, Bungener Laura, Daemen Toos, Wilschut Jan
Department of Medical Microbiology, Molecular Virology Section, University of Groningen, 9713 AV Groningen, The Netherlands.
Methods Enzymol. 2003;373:74-91. doi: 10.1016/S0076-6879(03)73005-5.
Influenza virosomes can be regarded as unilamellar liposomes carrying the spike proteins of influenza virus on their surface. Vaccination with influenza virosomes elicits high titers of influenza-specific antibodies, indicating that HA (and NA) reconstituted into a membranous environment exhibit strong immunogenicity. Moreover, virosomes can be used as presentation systems for unrelated antigens bound to the virosome surface. Because of their intrinsic adjuvant activity, virosomes support antibody formation and induction of T-helper cell responses against such surface-associated antigens. Provided that the fusogenic properties of the reconstituted HA are retained, virosomes can also be used to elicit cytotoxic T-cell responses against encapsulated antigens. Vaccines capable of activating the cellular branch of the immune response can be very important for protection against acute virus infections, especially for viruses with rapidly changing envelope glycoproteins like HIV and influenza virus. Moreover, virosomes can suit as powerful carriers in the development of prophylactic and immunotherapeutic strategies against cancer and premalignant disease. The use of virosomes as commercial influenza vaccine and as commercial adjuvant for a hepatitis A vaccine demonstrates that production of virosomes on an industrial scale is feasible, both technically and economically. The industrial production procedure currently followed has not been designed to retain the functional properties of HA. In fact, several steps in the procedure are probably incompatible with retention of fusion activity. As mentioned previously the fusogenic properties of virosomes are important for CTL activation and might also play a role in the induction of T-helper cell and antibody responses. Therefore, a number of key adaptations in the virosome production protocol will be necessary. Thus improved, virosomes are very attractive devices for the development of highly efficacious vaccines against a range of antigens.
流感病毒体可被视为单层脂质体，其表面携带流感病毒的刺突蛋白。用流感病毒体进行疫苗接种可引发高滴度的流感特异性抗体，这表明重构于膜环境中的血凝素（HA）（和神经氨酸酶（NA））具有很强的免疫原性。此外，病毒体可用作与病毒体表面结合的无关抗原的呈递系统。由于其固有的佐剂活性，病毒体可促进抗体形成以及针对此类表面相关抗原的辅助性T细胞反应的诱导。倘若重构的HA的融合特性得以保留，病毒体还可用于引发针对包封抗原的细胞毒性T细胞反应。能够激活免疫反应细胞分支的疫苗对于预防急性病毒感染可能非常重要，尤其是对于像HIV和流感病毒这类包膜糖蛋白快速变化的病毒。此外，在针对癌症和癌前疾病的预防和免疫治疗策略的开发中，病毒体可作为强大的载体。将病毒体用作商业流感疫苗以及甲型肝炎疫苗的商业佐剂表明，在技术和经济上，以工业规模生产病毒体都是可行的。目前遵循的工业生产程序并非旨在保留HA的功能特性。事实上，该程序中的几个步骤可能与融合活性的保留不相容。如前所述，病毒体的融合特性对于细胞毒性T淋巴细胞（CTL）激活很重要，并且可能在辅助性T细胞和抗体反应的诱导中也发挥作用。因此，在病毒体生产方案中进行一些关键调整将是必要的。经过如此改进后，病毒体对于开发针对一系列抗原的高效疫苗而言是非常有吸引力的工具。
