中文摘要：本研究通过小鼠模型证实，抗原复合物、载体（VLPs）和佐剂对B细胞免疫反应更为关键。研究采用了源于人类乳头状瘤病毒的E7蛋白作为抗原，该蛋白同时可以形成低聚物，分子量在158kDa 到10M Da之间，大小为50nm。通过化学反应或简单混合将E7低聚物与装载有CpGs的病毒样颗粒（VLPs）混合。当抗原与VLPs混合后增强了E7-特异性IgG反应。相比之下，抗原与VLPs混合后激发的CD4(+) 和CD8(+) T细胞反应以及T细胞介导抗肿瘤生长保护作用没有什么变化。该研究结果表明，为获得更好的免疫作用，必须将抗原与载体、佐剂联合使用才能激发更多的B细胞反应。
 
外文摘要：Since the discovery of the first virus-like particle (VLP) derived from hepatitis B virus in 1980 (1), the field has expanded substantially. Besides successful use of VLPs as safe autologous virus-targeting vaccines, the powerful immunogenicity of VLPs has been also harnessed to generate immune response against heterologous and even self-antigens (2-4). Linking adjuvants to VLPs displaying heterologous antigen ensures simultaneous delivery of all vaccine components to the same antigen-presenting cells. As a consequence, antigen-presenting cells, such as dendritic cells, will process and present the antigen displayed on VLPs while receiving costimulatory signals by the VLP-incorporated adjuvant. Similarly, antigen-specific B cells recognizing the antigen linked to the VLP are simultaneously exposed to the adjuvant. Here, we demonstrate in mice that physical association of antigen, carrier (VLPs), and adjuvant is more critical for B than T cell responses. As a model system, we used the E7 protein from human papilloma virus, which spontaneously forms oligomers with molecular weight ranging from 158 kDa to 10 MDa at an average size of 50 nm. E7 oligomers were either chemically linked or simply mixed with VLPs loaded with DNA rich in non-methylated CG motifs (CpGs), a ligand for toll-like receptor 9. E7-specific IgG responses were strongly enhanced if the antigen was linked to the VLPs. In contrast, both CD4(+) and CD8(+) T cell responses as well as T cell-mediated protection against tumor growth were comparable for linked and mixed antigen formulations. Therefore, our data show that B cell but not T cell responses require antigen-linkage to the carrier and adjuvant for optimal vaccination outcome.
外文关键词： VLPs； vaccines； HPV； CpG； adjuvant
作者：Gomes, AC; Flace, A; Saudan, P; Zabel, F; Cabral-Miranda, G; El Turabi, A; Manolova, V; Bachmann, MF
作者单位：牛津大学
期刊名称：FRONTIERS IN IMMUNOLOGY
期刊影响因子：5.695
出版年份：2017
出版刊次：3
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