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、农业微生物资源发掘与利用全国重点实验室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。
华中农业大学动物科学技术学院、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，华中农业大学为通讯作者单位。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
