Sun Wangyangji, Zhu Rui, Li Yu-An, Li Zewei, Du Yuanzhao, Wang Shifeng, Shi Huoying
College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu, China.
Jiangsu Co-Innovation Center for the Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, China.
Vet Res. 2025 Jul 21;56(1):154. doi: 10.1186/s13567-025-01590-0.
Salmonella enterica serovar Typhimurium (S. Typhimurium) vectors, which induce broad cellular and humoral immune responses, are excellent candidates for delivering foreign antigens. However, S. Typhimurium strains display limitations, including low levels of antigen protein expression when delivering viral antigens. In this study, we found that replacing the hemagglutinin (HA) precursor sequence of H9N2 AIV (avian influenza virus) with that from H7N9 AIV significantly improved HA protein expression. Building on this, we combined the H9N2 HA leader sequence with a tissue plasminogen activator (tPA) signal peptide and delayed lysis Salmonella mRNA interferase regulation vector (SIRV) system previously developed by our team. This novel approach markedly enhanced the expression of viral antigens delivered by Salmonella vectors. Our results demonstrate that both the H9N2 HA leader sequence and the tissue plasminogen activator (tPA) signal peptide significantly increased H7N9 AIV HA protein expression and substantially improved the protective efficacy of the attenuated S. Typhimurium vector delivering the H7N9 HA protein vaccine against H7N9 AIV challenge. These findings offer valuable insights for developing more effective attenuated Salmonella-based recombinant H7N9 AIV vaccines and provide a valuable reference for vaccine strategies against other infectious diseases.
肠炎沙门氏菌鼠伤寒血清型（鼠伤寒沙门氏菌）载体可诱导广泛的细胞免疫和体液免疫反应，是递送外源抗原的理想选择。然而，鼠伤寒沙门氏菌菌株存在局限性，包括在递送病毒抗原时抗原蛋白表达水平较低。在本研究中，我们发现用H7N9禽流感病毒（AIV）的血凝素（HA）前体序列替换H9N2 AIV的HA前体序列可显著提高HA蛋白表达。在此基础上，我们将H9N2 HA引导序列与组织纤溶酶原激活剂（tPA）信号肽以及我们团队先前开发的延迟裂解沙门氏菌mRNA干扰调节载体（SIRV）系统相结合。这种新方法显著增强了沙门氏菌载体递送的病毒抗原的表达。我们的结果表明，H9N2 HA引导序列和组织纤溶酶原激活剂（tPA）信号肽均显著增加了H7N9 AIV HA蛋白的表达，并大幅提高了递送H7N9 HA蛋白疫苗的减毒鼠伤寒沙门氏菌载体针对H7N9 AIV攻击的保护效力。这些发现为开发更有效的基于减毒沙门氏菌的重组H7N9 AIV疫苗提供了有价值的见解，并为针对其他传染病的疫苗策略提供了有价值的参考。
