南湖新闻网讯（通讯员 万加武）近日，我校动物科学技术学院、动物医学院赵凌教授团队研究成果以“CXCL13 promotes broad immune responses induced by circular RNA vaccines”为题在PNAS发表。研究提出了一种新型环状RNA疫苗设计思路，能够诱导针对多种病毒变体的交叉反应性抗体应答。
环状RNA是一种具有独特共价封闭结构的RNA分子，能够防止被外切酶降解，具有比传统线性mRNA更高的稳定性。这一特性弥补了普通mRNA疫苗在稳定性方面的不足，赋予其更广阔的应用前景。这种稳定的结构使得环状RNA能够更有效和持久地表达治疗性蛋白质或肽，展示了在疫苗研发和蛋白质替代疗法中的巨大潜力。
▲CircRNA疫苗设计和构建示意图
该研究设计了一个通用策略来提高环状RNA疫苗诱导的抗体反应的强度和广度——通过将趋化因子CXCL13和抗原整合到环状RNA中进行共表达来重塑淋巴结的免疫微环境。研究表明，CXCL13在淋巴结内促进生发中心形成，增强了体液免疫和细胞免疫反应。通过将CXCL13和抗原的共表达，CXCL13促进了针对流感病毒和新型冠状病毒的交叉反应性抗体的产生，在小鼠模型中实现了针对同源和异源流感病毒攻毒的保护。综上，该研究开发的基于环状RNA的抗原-CXCL13共表达系统提供了一个通用平台，该平台增强了针对流感病毒、新冠病毒和狂犬病毒等多种病原糖蛋白的抗体应答的强度和广度，突出了CXCL13在增强广泛免疫应答中的潜在功能。
米兰手机在线登入动物科学技术学院、动物医学院博士生万加武、王才茜为论文的第一作者，赵凌教授为论文的通讯作者，米兰手机在线登入为通讯作者单位。该研究得到了国家重点研发计划和中央高校基础研究项目的资助。
审核人：赵凌
英文摘要：Antibody responses induced by current vaccines for influenza and SARS-CoV-2 often lack robust cross-reactivity. As hubs where diverse immune cells converge and interact, the alterations in the immune microenvironment within lymph nodes (LNs) are intricately linked to immune responses. Herein, we designed a lipid nanoparticle (LNP) loaded with circular RNA (circRNA) and targeted to LNs, in which CXCL13 was directly integrated into antigen-encoding circRNA strands. We demonstrated that CXCL13 alters the transcriptomic profiles of LNs, especially the upregulation of IL-21 and IL-4. Meanwhile, CXCL13 promotes the formation of germinal center and elicits robust antigen-specific T cell responses. With the codelivery of CXCL13 and the antigen, CXCL13 enhances cross-reactive antibodies against influenza virus and SARS-CoV-2, achieving protection against both homologous and heterologous influenza virus challenges in a mouse model. Notably, the targeted modification of LNP surfaces with antibodies helps address some of the challenges associated with lyophilized LNP vaccines, which is crucial for the long-term storage of LNP-circRNA vaccines. Overall, the circRNA-based antigen-CXCL13 coexpression system developed herein provides a simple and robust platform that enhances the magnitude and breadth of antibody responses against multiple viral glycoproteins, highlighting the potential utility of CXCL13 in inducing broad immune responses.
论文链接：www.pnas.org/doi/10.1073/pnas.2406434121
