Blanas Athanasios, Karsjens Haiko, de Ligt Aafke, Huijbers Elisabeth J M, van Loon Karlijn, Denisov Stepan S, Durukan Canan, Engbersen Diederik J M, Groen Jan, Hennig Sven, Hackeng Tilman M, van Beijnum Judy R, Griffioen Arjan W
Angiogenesis Laboratory, Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands.
School for Cardiovascular Sciences, Department of Biochemistry, Maastricht University, Maastricht, the Netherlands.
iScience. 2022 Aug 19;25(8):104719. doi: 10.1016/j.isci.2022.104719. Epub 2022 Jul 5.
Poor immunogenicity of critical epitopes can hamper vaccine efficacy. To boost immune recognition of non- or low-immunogenic antigens, we developed a vaccine platform based on the conjugation of a target protein to a chimeric designer peptide (CDP) of bacterial origin. Here, we exploited this immune Boost (iBoost) technology to enhance the immune response against the receptor-binding domain (RBD) of the SARS-CoV-2 spike glycoprotein. Despite its fundamental role during viral infection, RBD is only moderately immunogenic. Immunization studies in mice showed that the conjugation of CDP to RBD induced superior immune responses compared to RBD alone. CDP-RBD elicited cross-reactive antibodies against the variants of concern Delta and Omicron. Furthermore, hamsters vaccinated with CDP-RBD developed potent neutralizing antibody responses and were fully protected from lung lesion formation upon challenge with SARS-CoV-2. In sum, we show that the iBoost conjugate vaccine technology provides a valuable tool for both quantitatively and qualitatively enhancing anti-viral immunity.
关键表位的免疫原性较差会妨碍疫苗效力。为增强对非免疫原性或低免疫原性抗原的免疫识别，我们开发了一种疫苗平台，该平台基于将靶蛋白与细菌来源的嵌合设计肽（CDP）偶联。在此，我们利用这种免疫增强（iBoost）技术来增强针对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）刺突糖蛋白受体结合域（RBD）的免疫反应。尽管RBD在病毒感染过程中起关键作用，但其免疫原性仅为中等水平。对小鼠的免疫研究表明，与单独的RBD相比，将CDP与RBD偶联可诱导更强的免疫反应。CDP-RBD引发了针对值得关注的变异株德尔塔和奥密克戎的交叉反应抗体。此外，用CDP-RBD疫苗接种的仓鼠产生了强效中和抗体反应，并且在用SARS-CoV-2攻击后完全免受肺部病变形成。总之，我们表明iBoost偶联疫苗技术为定量和定性增强抗病毒免疫力提供了一种有价值的工具。
