南湖新聞網訊（通訊員 萬(wan) 加武）近日，我校動物科學技術學院、動物醫學院趙淩教授團隊研究成果以“CXCL13 promotes broad immune responses induced by circular RNA vaccines”為(wei) 題在PNAS發表。研究提出了一種新型環狀RNA疫苗設計思路，能夠誘導針對多種病毒變體(ti) 的交叉反應性抗體(ti) 應答。
環狀RNA是一種具有獨特共價(jia) 封閉結構的RNA分子，能夠防止被外切酶降解，具有比傳(chuan) 統線性mRNA更高的穩定性。這一特性彌補了普通mRNA疫苗在穩定性方麵的不足，賦予其更廣闊的應用前景。這種穩定的結構使得環狀RNA能夠更有效和持久地表達治療性蛋白質或肽，展示了在疫苗研發和蛋白質替代療法中的巨大潛力。
▲CircRNA疫苗設計和構建示意圖
該研究設計了一個(ge) 通用策略來提高環狀RNA疫苗誘導的抗體(ti) 反應的強度和廣度——通過將趨化因子CXCL13和抗原整合到環狀RNA中進行共表達來重塑淋巴結的免疫微環境。研究表明，CXCL13在淋巴結內(nei) 促進生發中心形成，增強了體(ti) 液免疫和細胞免疫反應。通過將CXCL13和抗原的共表達，CXCL13促進了針對流感病毒和新型冠狀病毒的交叉反應性抗體(ti) 的產(chan) 生，在小鼠模型中實現了針對同源和異源流感病毒攻毒的保護。綜上，該研究開發的基於(yu) 環狀RNA的抗原-CXCL13共表達係統提供了一個(ge) 通用平台，該平台增強了針對流感病毒、新冠病毒和狂犬病毒等多種病原糖蛋白的抗體(ti) 應答的強度和廣度，突出了CXCL13在增強廣泛免疫應答中的潛在功能。
星空体育网站入口官网動物科學技術學院、動物醫學院博士生萬(wan) 加武、王才茜為(wei) 論文的第一作者，趙淩教授為(wei) 論文的通訊作者，星空体育网站入口官网為(wei) 通訊作者單位。該研究得到了國家重點研發計劃和中央高校基礎研究項目的資助。
審核人：趙淩
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.
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