Vaccine Development and Immunology/Vaccine Research Center, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
Protein Dynamics Group, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
Virology. 2022 Jan;566:89-97. doi: 10.1016/j.virol.2021.12.001. Epub 2021 Dec 3.
Virus-like particles (VLPs) modified through different molecular technologies are employed as delivery vehicles or platforms for heterologous antigen display. We have recently created a norovirus (NoV) VLP platform, where two influenza antigens, the extracellular domain of matrix protein M2 (M2e) or the stem domain of the major envelope glycoprotein hemagglutinin (HA2) are displayed on the surface of the NoV VLPs by SpyTag/SpyCatcher conjugation. To demonstrate the feasibility of the platform to deliver foreign antigens, this study examined potential interference of the conjugation with induction of antibodies against conjugated M2e peptide, HA2, and NoV VLP carrier. High antibody response was induced by HA2 but not M2e decorated VLPs. Furthermore, HA2-elicited antibodies did not neutralize the homologous influenza virus in vitro. Conjugated NoV VLPs retained intact receptor binding capacity and self-immunogenicity. The results demonstrate that NoV VLPs could be simultaneously used as a platform to deliver foreign antigens and a NoV vaccine.
病毒样颗粒(VLPs)经过不同的分子技术修饰后,可作为异源抗原展示的载体或平台。我们最近创建了一个诺如病毒(NoV)VLP 平台,在该平台中,通过 SpyTag/SpyCatcher 连接,将两种流感抗原,即基质蛋白 M2 的细胞外结构域(M2e)或主要包膜糖蛋白血凝素的茎结构域(HA2),展示在 NoV VLP 的表面。为了证明该平台传递外源抗原的可行性,本研究检查了连接对接枝 M2e 肽、HA2 和 NoV VLP 载体诱导抗体的潜在干扰。HA2 修饰的 VLPs 可诱导高抗体反应,但 M2e 修饰的 VLPs 则不能。此外,HA2 诱导的抗体不能中和体外同源流感病毒。连接的 NoV VLPs 保留了完整的受体结合能力和自身免疫原性。结果表明,NoV VLPs 可同时用作传递外源抗原和 NoV 疫苗的平台。