Schönfelder Jonathan, El Ayoubi Omar, Havryliuk Oles, Groß Rüdiger, Seidel Alina, Bakchoul Tamam, Münch Jan, Jumaa Hassan, Setz Corinna S
Institute of Immunology, Ulm University Medical Center, Ulm, Germany.
Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany.
Front Immunol. 2025 Apr 28;16:1570487. doi: 10.3389/fimmu.2025.1570487. eCollection 2025.
Efficient antibody responses are crucial for combating infectious diseases and vaccination remains a cornerstone of this effort. This study introduces a novel approach for enhancing immune responses in wild-type mice by utilizing pre-formed immune complexes, using the receptor-binding domain (RBD) of SARS-CoV-2 as a model antigen to illustrate the broader potential of the concept. Specifically, we found that pre-treating the antigen with bis-maleimide, a chemical linker that facilitates protein cross-linking, significantly enhances antibody production. Moreover, cross-linking of antigen to unrelated IgG using bis-maleimide generated immune complexes that markedly enhanced antigen-specific antibody responses, likely by mimicking natural memory-like mechanisms, suggesting that bis-maleimide pre-treated antigens may similarly engage IgG . In contrast, antigen crosslinking with IgA or IgM did not yield comparable effects, highlighting the unique capacity of IgG to boost immunogenicity. By leveraging the principles of immune memory, this study demonstrates the potential of pre-formed immune complexes to significantly enhance vaccine efficacy using an antigen-independent strategy broadly applicable to diverse pathogens.
高效的抗体反应对于对抗传染病至关重要，而疫苗接种仍然是这项工作的基石。本研究引入了一种新方法，通过利用预先形成的免疫复合物来增强野生型小鼠的免疫反应，以严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的受体结合域（RBD）作为模型抗原来说明这一概念的更广泛潜力。具体而言，我们发现用双马来酰亚胺（一种促进蛋白质交联的化学连接剂）预处理抗原可显著提高抗体产生。此外，使用双马来酰亚胺将抗原与无关的免疫球蛋白G（IgG）交联产生的免疫复合物显著增强了抗原特异性抗体反应，可能是通过模拟天然记忆样机制，这表明双马来酰亚胺预处理的抗原可能同样与IgG相互作用。相比之下，抗原与免疫球蛋白A（IgA）或免疫球蛋白M（IgM）交联未产生类似效果，突出了IgG增强免疫原性的独特能力。通过利用免疫记忆原理，本研究证明了预先形成的免疫复合物使用广泛适用于多种病原体的抗原非依赖性策略显著提高疫苗效力的潜力。
