Fredsgaard Laurits, Goksøyr Louise, Thrane Susan, Aves Kara-Lee, Theander Thor G, Sander Adam F
Centre for Medical Parasitology, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.
AdaptVac Aps, 2970 Hørsholm, Denmark.
Vaccines (Basel). 2021 May 21;9(6):539. doi: 10.3390/vaccines9060539.
Capsid virus-like particles (cVLPs) are used as molecular scaffolds to increase the immunogenicity of displayed antigens. Modular platforms have been developed whereby antigens are attached to the surface of pre-assembled cVLPs. However, it remains unknown to what extent the employed cVLP backbone and conjugation system may influence the immune response elicited against the displayed antigen. Here, we performed a head-to-head comparison of antigen-specific IgG responses elicited by modular cVLP-vaccines differing by their employed cVLP backbone or conjugation system, respectively. Covalent antigen conjugation (i.e., employing the SpyTag/SpyCatcher system) resulted in significantly higher antigen-specific IgG titers compared to when using affinity-based conjugation (i.e., using biotin/streptavidin). The cVLP backbone also influenced the antigen-specific IgG response. Specifically, vaccines based on the bacteriophage AP205 cVLP elicited significantly higher antigen-specific IgG compared to corresponding vaccines using the human papillomavirus major capsid protein (HPV L1) cVLP. In addition, the AP205 cVLP platform mediated induction of antigen-specific IgG with a different subclass profile (i.e., higher IgG2a and IgG2b) compared to HPV L1 cVLP. These results demonstrate that the cVLP backbone and conjugation system can individually affect the IgG response elicited against a displayed antigen. These data will aid the understanding and process of tailoring modular cVLP vaccines to achieve improved immune responses.
衣壳病毒样颗粒（cVLPs）被用作分子支架，以增强展示抗原的免疫原性。已经开发出模块化平台，通过该平台将抗原附着到预先组装的cVLPs表面。然而，所使用的cVLP骨架和偶联系统在多大程度上可能影响针对展示抗原引发的免疫反应仍不清楚。在这里，我们对分别因所使用的cVLP骨架或偶联系统不同而有所差异的模块化cVLP疫苗引发的抗原特异性IgG反应进行了直接比较。与使用基于亲和力的偶联（即使用生物素/链霉亲和素）相比，共价抗原偶联（即采用SpyTag/SpyCatcher系统）导致抗原特异性IgG滴度显著更高。cVLP骨架也影响抗原特异性IgG反应。具体而言，与使用人乳头瘤病毒主要衣壳蛋白（HPV L1）cVLP的相应疫苗相比，基于噬菌体AP205 cVLP的疫苗引发的抗原特异性IgG显著更高。此外，与HPV L1 cVLP相比，AP205 cVLP平台介导诱导出具有不同亚类谱（即更高的IgG2a和IgG2b）的抗原特异性IgG。这些结果表明，cVLP骨架和偶联系统可分别影响针对展示抗原引发的IgG反应。这些数据将有助于理解和定制模块化cVLP疫苗以实现改善免疫反应的过程。
