Zhang Chunhe, Li Fangshen, Yu Xin, Tian Haochen, Li Yiyang, Liu Xinyao, Liu Wenmo, Yu Bin, Qiao Zhen-An, Yu Xianghui
National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, China.
National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, China.
Acta Biomater. 2025 Jan 24;193:362-376. doi: 10.1016/j.actbio.2024.12.056. Epub 2024 Dec 25.
Effective vaccination is crucial for intervening in the COVID-19 pandemic. However, with the continuous mutation of the SARS-CoV-2, existing vaccines including subunit vaccines cannot effectively prevent virus infections. Hence, there is an urgent need to enhance the immunogenicity of existing vaccines to induce a more potent and durable immune response. We previously found that periodic mesoporous organosilica (PMO) could act as a potential nanoadjuvant for subunit vaccines, eliciting potent antigen-specific germinal center (GC) responses by activating naïve B cells. In this study, we describe the design of PMO decorated with TDB, a potent Macrophage-induced C-type lectin (Mincle) agonist, to improve the adjuvanticity of PMO for COVID-19 vaccines. We found that the TDB@PMO adjuvant can effectively deliver antigens to lymph nodes and promote antigen uptake by immune cells. More importantly, the TDB@PMO adjuvant vaccine could activate the innate immune of both naïve B cells and dendritic cells via the Mincle signaling pathway, and further enhance the GC responses and resulting in potent SARS-CoV-2 specific humoral and cellular immune responses. Overall, we have developed an effective and safe nanoadjuvant platform, laying the foundation for the design and development of subunit vaccines against pathogens such as SARS-CoV-2. STATEMENT OF SIGNIFICANCE: Adjuvants play a crucial role in enhancing the effectiveness of vaccines by boosting the immune response. The emergence of highly mutated viruses, such as coronaviruses, has presented new requirements for adjuvant design. This work designed a nanoadjuvant platform, TDB@PMO, to enhance the immune response of the COVID-19 subunit vaccine. The result demonstrated that TDB@PMO nanoadjuvant can simultaneously boost the activation effects of B cells and DC cells through the Mincle signaling pathway. Furthermore, immunization with TDB@PMO-RBD nanoadjuvanted vaccine in mice significantly enhanced germinal center responses and antibody production, while also eliciting a robust antigen-specific T cell immune response in spleen. This design provided a reference for the development of next-generation virus subunit vaccines.
有效的疫苗接种对于干预新冠疫情至关重要。然而，随着严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的不断变异，包括亚单位疫苗在内的现有疫苗无法有效预防病毒感染。因此，迫切需要增强现有疫苗的免疫原性，以诱导更有效和持久的免疫反应。我们之前发现，周期性介孔有机硅（PMO）可作为亚单位疫苗的潜在纳米佐剂，通过激活初始B细胞引发强大的抗原特异性生发中心（GC）反应。在本研究中，我们描述了用TDB（一种有效的巨噬细胞诱导C型凝集素（Mincle）激动剂）修饰的PMO的设计，以提高PMO对新冠疫苗的佐剂活性。我们发现，TDB@PMO佐剂可有效将抗原递送至淋巴结，并促进免疫细胞对抗原的摄取。更重要的是，TDB@PMO佐剂疫苗可通过Mincle信号通路激活初始B细胞和树突状细胞的固有免疫，进一步增强GC反应，并产生强大的SARS-CoV-2特异性体液和细胞免疫反应。总体而言，我们开发了一个有效且安全的纳米佐剂平台，为设计和开发针对SARS-CoV-2等病原体的亚单位疫苗奠定了基础。重要性声明：佐剂通过增强免疫反应在提高疫苗效力方面发挥着关键作用。冠状病毒等高变异病毒的出现对佐剂设计提出了新要求。这项工作设计了一个纳米佐剂平台TDB@PMO，以增强新冠亚单位疫苗的免疫反应。结果表明，TDB@PMO纳米佐剂可通过Mincle信号通路同时增强B细胞和DC细胞的激活作用。此外，用TDB@PMO-RBD纳米佐剂疫苗免疫小鼠可显著增强生发中心反应和抗体产生，同时在脾脏中引发强大的抗原特异性T细胞免疫反应。该设计为下一代病毒亚单位疫苗的开发提供了参考。
